Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relie...Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relieving pain, promoting blood circulation, removing blood stasis, and softening hardness to dissipate stagnation, and show definite curative effect in preventing and treating breast diseases. Nano-composite hydrogels have the advantages of small toxic and side effects, high bioavailability, high targeting and controllable drug release. Therefore, this paper summarized and analyzed relevant literature of Zhuang medicine in treating breast diseases and clinical research of nanogels, providing new ideas and scientific basis for the treatment of mastitis with Zhuang medicine combined with nanogels.展开更多
A series of branched polyethylenimine(PEI) modifications including PEGylation(PEG2 k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2 k-PEI-ss nanogels and subsequent carboxymethylation(PEG2 ...A series of branched polyethylenimine(PEI) modifications including PEGylation(PEG2 k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2 k-PEI-ss nanogels and subsequent carboxymethylation(PEG2 k-CMPEI-ss) for modulation of the polymer pk a have been introduced for cellular delivery of Anti-mi R-21. The synthesis was characterized using 1 H NMR, FTIR, TNBS, potentiometric titration, particle size and ζ potential. Loading of Anti-mi R-21 at various N/P ratios was investigated by gel retardation, ethidium bromide dye exclusion, heparin sulfate competition and DNase I digestion experiments. The mi R-21 silencing was measured by stem-loop RT PCR in A2780 ovarian cancer cell lines whether it is sensitive to resistant to cisplatin. It has been shown that PEG2 k-CMPEI-ss was well suited for delivery of Anti-mi R-21 in terms of nucleic acid loading, preservation against extracellular matrix and nucleases and sequence-specific silencing of mi RNA-21 in vitro. Moreover, it has been demonstrated that pre-treating cells with Anti-mi R-21 loaded nanogels can sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2 k-CMPEIss mediated micro RNA delivery can be considered as a novel strategy for ovarian cancer therapy.展开更多
A novel method has been successfully developed for the facile and efficient removal of organic micro-pollutants(OMP)from water based on novel functional capsules encapsulating molecular-recognizable nanogels.The funct...A novel method has been successfully developed for the facile and efficient removal of organic micro-pollutants(OMP)from water based on novel functional capsules encapsulating molecular-recognizable nanogels.The functional capsules are composed of ultrathin calcium alginate(Ca-Alg)hydrogel shells as semipermeable membranes and encapsulated poly(N-isopropylacrylamide-co-acrylic acid-g-mono-(6-ethanediamine-6-deoxy)-β-cyclodextrin)(PNCD)nanogels withβ-cyclodextrin(CD)moieties as OMP capturers.The semipermeable membranes of the capsules enable the free transfer of OMP and water molecules across the capsule shells,but confine the encapsulated PNCD nanogels within the capsules.Bisphenol A(BPA),an endocrine-disrupting chemical that is released from many plastic water containers,was chosen as a model OMP molecule in this study.Based on the host–guest recognition complexation,the CD moieties in the PNCD nanogels can efficiently capture BPA molecules.Thus,the facile and efficient removal of BPA from water can be achieved by immersing the proposed functional capsules into BPA-containing aqueous solutions and then simply removing them,which is easily done due to the capsules’characteristically large size of up to several millimeters.The kinetics of adsorption of BPA molecules by the capsules is well described by a pseudo-second-order kinetic model,and the isothermal adsorption thermodynamics align well with the Freundlich and Langmuir isothermal adsorption models.The regeneration of capsules can be achieved simply by washing them with water at temperatures above the volume phase transition temperature of the PNCD nanogels.Thus,the proposed functional capsules encapsulating molecular-recognizable nanogels provide a novel strategy for the facile and efficient removal of OMP from water.展开更多
Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specifi...Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specific(targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated(25 °C/60% RH) and long-term(5 °C) stability of DNGs prepared with formaldehyde(FDNGs) and glyoxal(GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared(initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different(p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.展开更多
Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhes...Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhesion.The ability to manipulate this ligand-mediated cell adhesion process is crucial for regulating cell migration,cell differentiation,injury healing,and immune response.Some recent studies reported the importance of the tether length/mobility of the cell adhesive ligands in regulating the traction force development of cells.In the native cellular microenvironment,such a dynamic change in the nanoscale tether length of bioactive ligands is often mediated by conformational changes of the structural proteins due to protein folding or degradation.However,no prior studies have demonstrated the modulation of the ligand tether mobility by controlling the intramolecular folding of polymeric linkers.Unfoldable synthetic macromolecules with easy synthetic routes and controllable structures,such as supramolecular host-guest single chain nanogels(SCNGs),are ideal candidates for mimicking the changes in the tether mobility of bioactive ligands via biorthogonal triggers.Methods S,S’-bis(a’a’-dimethyl-a’’-propargyl acetate)trithiocarbonate was first used to mediate the RAFT polymerization of N,N-dimethyl acrylamide,vinyl-adamantane and vinyl-β-cyclodextrin to yield the ADA@CD-SCNGs.The preparation of the unfoldable host-guest SCNGs was evidenced by the by gel permeation chromatography,proton nuclear magnetic resonance spectroscopy,atomic force microscopy and dynamic light scattering.Then the RGD peptide was conjugated to the alkynyl group on one end of the SCNGs before immobilizing the material on the substrate,which was confirmed by scanning electron microscopy(SEM).The regulation of cell behaviours by unfolding of the SCNG-RGD was confirmed by immunofluorescence staining of vinculin and Yes-associated protein(YAP).Results The preparation of ADA@CD-SCNGs was confirmed by GPC which showed a unimodal molecular weight distribution.DLS and AFM data also proved that the SCNGs had an average diameter of 12±3nm.SEM images showed that SCNGs were conjugated as a linker of RGD peptide to thiolated glass substrate at an average density of 162±11 particles/μm2.These particles disappeared after adding free competitive ADA guest molecules,indicating the triggered unfolding of the tether SCNGs.In addition,the unfolding of supramolecular ADA@CD-SCNGs was also evidenced by a decrease in the GPC elution time and a slight increase in the apparent molecular weight.These results show that the immobilized ADA@CD-SCNGs can be unfolded to tune the tether length and mobility of the conjugated RGD ligands.Then we investigated the regulation of the cell behaviors on the substrate by triggering the unfolding of SCNG linkers.A critical level of traction force is required to effectively initiate and maintain integrin-mediated formation of FA complexes and subsequent mechano-transduction signaling.An increased tether length in cell-adhesive ligands can lead to a diminished cell traction force as if cells are adhering to soft substrates.Here,the unfolding of the ADA@CD-SCNG-RGD triggered by the addition of free ADA led to disassembly of the mature focal adhesions in the cells as evidenced by the reduced vinculin and F-actin in staining.Subsequently,nuclear YAP also decreased significantly because of the impaired mechano-sensing and diminished cell cytoskeleton tension.In addition,the extensively spread cells gradually became round after the medium was supplemented with free competitive ADA to unfold the SCNG linker.These finding demonstrates that the substrates with the unfolded ADA@CD-SCNG-RGD only supported weak cell adhesions.In contrast,on the substrate conjugated with the nonunfoldable MBA-SCNG-RGD linker,the addition of free ADA resulted in no change in the spread cell morphology and protein expressions.These results indicate that the unfoldable host-guest ADA@CD-SCNG can be used to manipulate the nanoscale presentation of ligands to regulate cell behaviors.Conclusions We demonstrate the application of SCNGs as the supramolecular linker to tune the nanoscale ligand tether length.These findings demonstrate that the strategy of manipulating the tether mobility of bioactive ligands by using supramolecular SCNGs as linkers provides a highly tunable,biomimetic,and bio-orthogonal approach to study the dynamic events of cell adhesion.展开更多
Achieving the reuse of traditional egg by-products,salted duck egg whites(SEW),is an urgent problem to be solved.In this current work,we constructed a heat-induced gel-assisted desalination method for SEW.Subsequently...Achieving the reuse of traditional egg by-products,salted duck egg whites(SEW),is an urgent problem to be solved.In this current work,we constructed a heat-induced gel-assisted desalination method for SEW.Subsequently,a top-down way was utilized to prepare desalted duck egg protein nanogels(DEPN)with uniformly distributed diameters and their application in the oil/water(O/W)interface system was explored.The results revealed that the increase of DEPN concentration could lower the droplet size,however,the size was negatively correlated with the oil phase fraction.Moreover,the effect of pH,ionic strength,and temperature on the emulsion stability demonstrated that the DEPN-stabilized emulsion displayed superior physical stability under different conditions.The addition of NaCl resulted in the significant decrease in droplet size of the emulsion,while further increasing the NaCl concentration,the droplet size did not decrease accordingly.Besides,heat-treatment and cold-treatment had little negative effect on the stability of the emulsion.Even if the droplet size of the emulsion increased at 80℃for 3 h,the morphology of the emulsion remained unchanged.Our study demonstrated DEPN had great potential as a stabilizer for food-grade Pickering emulsions.展开更多
One-pot synthesis of magnetic nanogels via photochemical method is reported in this paper. Poly(2-hydroxyethyl methacrylate)(PHEMA) magnetic nanogels are synthesized by in-situ polymeriza-tion of 2-hydroxyethyl methac...One-pot synthesis of magnetic nanogels via photochemical method is reported in this paper. Poly(2-hydroxyethyl methacrylate)(PHEMA) magnetic nanogels are synthesized by in-situ polymeriza-tion of 2-hydroxyethyl methacrylate(HEMA) and N,N'-methylene-bis-(acrylamide)(MBA) in Fe3O4 aqueous suspension under UV irradiation. The structure and compositions of magnetic nanogels are characterized by FTIR,TGA,SEM,TEM and PCS. TGA measurement indicates that magnetic nanogels contain 90% magnetite. Both naked Fe3O4 and magnetic nanogels are superparamagnatic at room temperature according to magnetization curves. The swollen capability of the hydrogel shell is proved by contrasting the particles sizes obtained by SEM,TEM and PCS. Particle diameters can be manipu-lated by changing monomer concentration and irradiation time. A mechanism of the coating process is proposed.展开更多
The implementation of nanotechnology to develop efficient antimicrobial systems has a significant impact on the prospects of the biomedical field.Nanogels are soft polymeric particles with an internally cross-linked s...The implementation of nanotechnology to develop efficient antimicrobial systems has a significant impact on the prospects of the biomedical field.Nanogels are soft polymeric particles with an internally cross-linked structure,which behave as hydrogels and can be reversibly hydrated/dehydrated(swollen/shrunken)by the dispersing solvent and external stimuli.Their excellent properties,such as biocompatibility,colloidal stability,high water content,desirable mechanical properties,tunable chemical functionalities,and interior gel-like network for the incorporation of biomolecules,make them fascinating in the field of biological/biomedical applications.In this review,various approaches will be discussed and compared to the newly developed nanogel technology in terms of efficiency and applicability for determining their potential role in combating infections in the biomedical area including implant-associated infections.展开更多
One-pot synthesis of magnetic nanogels with excellent biocompatibility via the photochemical method is reported in this paper.Poly(PEGMA) modified superparamagnetic nanogels(poly(PEGMA) magnetic nanogels) were synthes...One-pot synthesis of magnetic nanogels with excellent biocompatibility via the photochemical method is reported in this paper.Poly(PEGMA) modified superparamagnetic nanogels(poly(PEGMA) magnetic nanogels) were synthesized by in-situ polymerization using poly(ethylene glycol) methacrylate(PEGMA) as the monomer and N,N'-methylene-bis-(acrylamide)(MBA) as the cross-linking agent in magnetite aqueous suspension under UV irradiation.The surface functional groups and components of magnetic nanogels were analyzed by Fourier transform infrared spectroscopy(FTIR) and a thermogra-vimetric analyzer(TGA).The results indicated that the poly(PEGMA) magnetic nanogels were synthe-sized successfully by coating poly(PEGMA) on the Fe3O4 nanoparticles under UV irradiation,and the Fe3O4 nanoparticles content in this nanogels was above 50 wt%.The morphology,size,zeta-potential and magnetic property were also characterized.The magnetic nanogels had a nearly spherical shape and core-shell structure,the average size in aqueous system measured by photon correlation spec-troscopy(PCS) was 68.4 nm,which was much bigger than that in the dry state,the nanogels behaved superparamagnetically with saturated magnetization of 58.6 emu/g,and the zeta-potential was-16.3-_17.3 mV at physiological pH(6.8-7.4) which could help to maintain stability in blood.The preliminary application as drug carrier was made and the doxorubicin-loaded magnetic nanogels had an excellent property in slow-release.The experiment indicated that the magnetic nanogel was an ideal candidate carrier in target drug delivery systems and other biomedical application.展开更多
Nanogels (NGs) as soft nanosized materials have gained a variety of interests in biomedical fields. The versatile NG scaffolds with 3-dimensional spherical shape, high loading efficiency, tunable surface functionali...Nanogels (NGs) as soft nanosized materials have gained a variety of interests in biomedical fields. The versatile NG scaffolds with 3-dimensional spherical shape, high loading efficiency, tunable surface functionalization, and excellent biocompatibility afford their uses as carrier to load mono- or multi-mode molecular imaging contrast agents (CAs). This review summarizes the synthesis routes and applications of NGs as CAs for molecular imaging applications including magnetic resonance (MR), computed tomography (CT), radionuclide, optical, and dual/mul- ti-modality imaging.展开更多
Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and en...Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.展开更多
A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability.The fluorescent nanogels display excellent biodegradability and cytocompat...A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability.The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free onepot reaction,derived entirely from biocompatible monomers citric acid,maleic acid,L-cysteine,and poly(ethylene glycol).The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity,and demonstrate long-term structural stability in biological buffer for two weeks.To gauge potential in theranostic applications,the fluorescent nanogels were surface functionalized with biologically active RGD peptides and encapsulated with active anti-cancer drug Doxorubicin,resulting in a pH-responsive controlled drug release in acidic pH resembling tumor environments.The strong fluorescence of the nanogels enabled tracking of targeted drug delivery,showing that drug-loaded nanogels homed into the cytoplasmic regions of prostate cancer cells to significantly induce cell death.These photo-crosslinkable and biodegradable nanogels pose as a strong candidate for theranostic medicine,demonstrating versatile functionalization,high stability in biological buffers,and capacity for real-time fluorescence-based monitoring of targeted drug delivery.展开更多
Carbon nanogels(CNGs)with dual ability of reactive oxygen species(ROS)imaging and photodynamic therapy have been designed with selfassembled chemiluminescent carbonized polymer dots(CPDs).With efficient deep-red/near-...Carbon nanogels(CNGs)with dual ability of reactive oxygen species(ROS)imaging and photodynamic therapy have been designed with selfassembled chemiluminescent carbonized polymer dots(CPDs).With efficient deep-red/near-infrared chemiluminescence(CL)emission and distinctive photodynamic capacity,the H2O2-driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors,enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high-performance therapy for xenograft tumors.Mechanistically,ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2,enabling in vivo CL imaging.Meanwhile,part of the excited-state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen,endowing the apoptosis of tumor cells and thus enabling cancer therapy.These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents.展开更多
In this study, a networked swellable dextrin nanogel (DNG) was developed to achieve stimulated responsive small interfering RNA (siRNA) release for melanoma tumor therapy, siRNA was loaded into multidimensional de...In this study, a networked swellable dextrin nanogel (DNG) was developed to achieve stimulated responsive small interfering RNA (siRNA) release for melanoma tumor therapy, siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione- triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery.展开更多
For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs...For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.展开更多
Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulat...Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.展开更多
A series of thermoresponsive cationic dendronized copolymers and their corresponding nano gels containing den dritic oligoethylene glycol(OEG)units and guanidine groups were prepared,and their complexation,protect!on,...A series of thermoresponsive cationic dendronized copolymers and their corresponding nano gels containing den dritic oligoethylene glycol(OEG)units and guanidine groups were prepared,and their complexation,protect!on,and release of nucleic acids were investigated.The dendritic OEGs endow these copolymer materials with good biocompatibility and characteristic thermoresponsiveness,while cationic guanidine groups can efficiently bind with the nucleic acids.The dendritic topology also affords the copolymers specific shielding effect which plays an essential role in protecting the activity of nucleic acids.At room temperature,dendronized copolymers and the corresponding nanogels could efficiently capture and condense the nucleic acids,while above their cloud points(Tcps),more than 75%of siRNA could be released in 1 h triggered by ATP.More importantly,the copolymer showed protective capability to siRNA,while nano gels exhibit even better protection when compared to the copolymers due to the synergetic effect from the three-dimensional cross-linked network and high density of dendritic units in vicinity.This kind of smart dendr on ized copolymer nano gels form a no vel class of scaffolds as promisi ng materials for biomedical applicatio ns.展开更多
The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to dia...The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to diagnostic ultrasound(US)of 2 MHz.Herein,we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery(MCA).Via intravenous(i.v.)administration,the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation,leading to enhanced thrombolysis efficiency of the nUK,evidenced from smaller infarct volume and better clinical scores when compared to the i.v.dose of free uPA no matter with or without US intervention.Meanwhile,the preservation ability of the nanogels not only prolonged the circulation duration of the protein,but also resulted in the better blood-brain barrier protection of the nUK formulation,showing no increased risk on the hemorrhagic transformation than the controls.This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.展开更多
Although targeted therapy and immunotherapy are now shining in the treatment of some cancers,chemotherapy is still the cornerstone of drug treatment for many cancer patients.The emergence of chemotherapy prodrugs can ...Although targeted therapy and immunotherapy are now shining in the treatment of some cancers,chemotherapy is still the cornerstone of drug treatment for many cancer patients.The emergence of chemotherapy prodrugs can improve the drug activity and reduce the side effects of chemotherapy.When used,the tumor microenvironment has characteristics different from normal tissues,and the existence of the microenvironment provided a more convenient way to design responsive nanodrugs.Herein,we designed a glutathione(GSH)-responsive prodrug nanogels for enhancing tumor chemotherapy.In the nanogels of HHNP,10-hydroxycamptothecin(HCPT)played an essential role in killing cancer cells.HCPT was jointed with a cross-linker agent with disulfide bond and was further coated with polyethylene glycol,which not only prolonged the half-life of the drug,but also made HCPT accurate transport to the tumor fractions and achieved precise and controllable release.The proposal of HHNP effectively retained the biological activity of the drug,and introduced functions such as targeting,selective release and biodegradation,which greatly improved the medical efficiency of the drug and effectively reduced the toxic and side effects.This chemotherapeutic prodrug nanogel offers a new window for constructing efficient drug delivery platform.展开更多
Nanogels hold promise as soft and functional carriers and nanoreactors,but whether they will ever reach the stage of large-scale application depends crucially on efficient production methods,and on what interesting pr...Nanogels hold promise as soft and functional carriers and nanoreactors,but whether they will ever reach the stage of large-scale application depends crucially on efficient production methods,and on what interesting properties and functionalities they can have.In particular,nanogels consisting of highly charged polyelectrolyte have not yet been very much explored.Here,the authors present a novel and generic strategy for controlled and efficient synthesis of a large diversity of polyelectrolyte nanogels.The method is based on polymerizing an ionic monomer in the presence of an oppositely charged polyion-neutral diblock copolymer as template,while adding a cross-linker.The growing polymer chains assemble with the template,forming polyion complex micelles,which dissociate upon increasing salt concentration.Subsequent separation yields nanogels with well-controlled size and properties,and free template polymers that can be used again.Our design can be applied generally to a wide range of both cationic and anionic monomers,as well as various cross-linkers.Scaled-up production presents no problems as increasing monomer concentration(hundreds of mM)and reaction volume(up to 1 L)hardly compromise product quality.Moreover,the obtained nanogels with their well-controlled size,morphology,chemistry,and cross-linking degree perform well as soft nanocarriers and catalytic nanoreactors.展开更多
基金Supported by Undergraduate Training Program for Innovation and Entrepreneurship of Guangxi University of Chinese Medicine in 2023(S202310600116)。
文摘Mastitis is a common and frequently-occurring disease among Chinese women, which seriously harms their mental and physical health. External application of Zhuang medicine has the effects of dredging collaterals, relieving pain, promoting blood circulation, removing blood stasis, and softening hardness to dissipate stagnation, and show definite curative effect in preventing and treating breast diseases. Nano-composite hydrogels have the advantages of small toxic and side effects, high bioavailability, high targeting and controllable drug release. Therefore, this paper summarized and analyzed relevant literature of Zhuang medicine in treating breast diseases and clinical research of nanogels, providing new ideas and scientific basis for the treatment of mastitis with Zhuang medicine combined with nanogels.
基金This work was supported financially by Shiraz University of Medical Sciences(Grant No:SUMS-93-01-05-8630)The facility supports of"Center for Nanotechnology in Drug Delivery"are gratefully acknowledged.
文摘A series of branched polyethylenimine(PEI) modifications including PEGylation(PEG2 k-PEI) for steric shielding, redox-sensitive crosslinking for synthesis PEG2 k-PEI-ss nanogels and subsequent carboxymethylation(PEG2 k-CMPEI-ss) for modulation of the polymer pk a have been introduced for cellular delivery of Anti-mi R-21. The synthesis was characterized using 1 H NMR, FTIR, TNBS, potentiometric titration, particle size and ζ potential. Loading of Anti-mi R-21 at various N/P ratios was investigated by gel retardation, ethidium bromide dye exclusion, heparin sulfate competition and DNase I digestion experiments. The mi R-21 silencing was measured by stem-loop RT PCR in A2780 ovarian cancer cell lines whether it is sensitive to resistant to cisplatin. It has been shown that PEG2 k-CMPEI-ss was well suited for delivery of Anti-mi R-21 in terms of nucleic acid loading, preservation against extracellular matrix and nucleases and sequence-specific silencing of mi RNA-21 in vitro. Moreover, it has been demonstrated that pre-treating cells with Anti-mi R-21 loaded nanogels can sensitize them to cis-Pt even at non-toxic concentraions. The results indicate that PEG2 k-CMPEIss mediated micro RNA delivery can be considered as a novel strategy for ovarian cancer therapy.
基金The authors gratefully acknowledge support from the National Natural Science Foundation of China(21991101).
文摘A novel method has been successfully developed for the facile and efficient removal of organic micro-pollutants(OMP)from water based on novel functional capsules encapsulating molecular-recognizable nanogels.The functional capsules are composed of ultrathin calcium alginate(Ca-Alg)hydrogel shells as semipermeable membranes and encapsulated poly(N-isopropylacrylamide-co-acrylic acid-g-mono-(6-ethanediamine-6-deoxy)-β-cyclodextrin)(PNCD)nanogels withβ-cyclodextrin(CD)moieties as OMP capturers.The semipermeable membranes of the capsules enable the free transfer of OMP and water molecules across the capsule shells,but confine the encapsulated PNCD nanogels within the capsules.Bisphenol A(BPA),an endocrine-disrupting chemical that is released from many plastic water containers,was chosen as a model OMP molecule in this study.Based on the host–guest recognition complexation,the CD moieties in the PNCD nanogels can efficiently capture BPA molecules.Thus,the facile and efficient removal of BPA from water can be achieved by immersing the proposed functional capsules into BPA-containing aqueous solutions and then simply removing them,which is easily done due to the capsules’characteristically large size of up to several millimeters.The kinetics of adsorption of BPA molecules by the capsules is well described by a pseudo-second-order kinetic model,and the isothermal adsorption thermodynamics align well with the Freundlich and Langmuir isothermal adsorption models.The regeneration of capsules can be achieved simply by washing them with water at temperatures above the volume phase transition temperature of the PNCD nanogels.Thus,the proposed functional capsules encapsulating molecular-recognizable nanogels provide a novel strategy for the facile and efficient removal of OMP from water.
文摘Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specific(targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated(25 °C/60% RH) and long-term(5 °C) stability of DNGs prepared with formaldehyde(FDNGs) and glyoxal(GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared(initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different(p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.
文摘Objective The binding of cell adhesive peptides(such as RGD)to integrins initiates the recruitment of cytoplasmic adaptor proteins(e.g.,vinculin)and the formation of focal adhesion(FA)complexes required for cell adhesion.The ability to manipulate this ligand-mediated cell adhesion process is crucial for regulating cell migration,cell differentiation,injury healing,and immune response.Some recent studies reported the importance of the tether length/mobility of the cell adhesive ligands in regulating the traction force development of cells.In the native cellular microenvironment,such a dynamic change in the nanoscale tether length of bioactive ligands is often mediated by conformational changes of the structural proteins due to protein folding or degradation.However,no prior studies have demonstrated the modulation of the ligand tether mobility by controlling the intramolecular folding of polymeric linkers.Unfoldable synthetic macromolecules with easy synthetic routes and controllable structures,such as supramolecular host-guest single chain nanogels(SCNGs),are ideal candidates for mimicking the changes in the tether mobility of bioactive ligands via biorthogonal triggers.Methods S,S’-bis(a’a’-dimethyl-a’’-propargyl acetate)trithiocarbonate was first used to mediate the RAFT polymerization of N,N-dimethyl acrylamide,vinyl-adamantane and vinyl-β-cyclodextrin to yield the ADA@CD-SCNGs.The preparation of the unfoldable host-guest SCNGs was evidenced by the by gel permeation chromatography,proton nuclear magnetic resonance spectroscopy,atomic force microscopy and dynamic light scattering.Then the RGD peptide was conjugated to the alkynyl group on one end of the SCNGs before immobilizing the material on the substrate,which was confirmed by scanning electron microscopy(SEM).The regulation of cell behaviours by unfolding of the SCNG-RGD was confirmed by immunofluorescence staining of vinculin and Yes-associated protein(YAP).Results The preparation of ADA@CD-SCNGs was confirmed by GPC which showed a unimodal molecular weight distribution.DLS and AFM data also proved that the SCNGs had an average diameter of 12±3nm.SEM images showed that SCNGs were conjugated as a linker of RGD peptide to thiolated glass substrate at an average density of 162±11 particles/μm2.These particles disappeared after adding free competitive ADA guest molecules,indicating the triggered unfolding of the tether SCNGs.In addition,the unfolding of supramolecular ADA@CD-SCNGs was also evidenced by a decrease in the GPC elution time and a slight increase in the apparent molecular weight.These results show that the immobilized ADA@CD-SCNGs can be unfolded to tune the tether length and mobility of the conjugated RGD ligands.Then we investigated the regulation of the cell behaviors on the substrate by triggering the unfolding of SCNG linkers.A critical level of traction force is required to effectively initiate and maintain integrin-mediated formation of FA complexes and subsequent mechano-transduction signaling.An increased tether length in cell-adhesive ligands can lead to a diminished cell traction force as if cells are adhering to soft substrates.Here,the unfolding of the ADA@CD-SCNG-RGD triggered by the addition of free ADA led to disassembly of the mature focal adhesions in the cells as evidenced by the reduced vinculin and F-actin in staining.Subsequently,nuclear YAP also decreased significantly because of the impaired mechano-sensing and diminished cell cytoskeleton tension.In addition,the extensively spread cells gradually became round after the medium was supplemented with free competitive ADA to unfold the SCNG linker.These finding demonstrates that the substrates with the unfolded ADA@CD-SCNG-RGD only supported weak cell adhesions.In contrast,on the substrate conjugated with the nonunfoldable MBA-SCNG-RGD linker,the addition of free ADA resulted in no change in the spread cell morphology and protein expressions.These results indicate that the unfoldable host-guest ADA@CD-SCNG can be used to manipulate the nanoscale presentation of ligands to regulate cell behaviors.Conclusions We demonstrate the application of SCNGs as the supramolecular linker to tune the nanoscale ligand tether length.These findings demonstrate that the strategy of manipulating the tether mobility of bioactive ligands by using supramolecular SCNGs as linkers provides a highly tunable,biomimetic,and bio-orthogonal approach to study the dynamic events of cell adhesion.
基金financially supported by the National Natural Science Foundation of China(Grant No.32172354)the Opening Project of Key Laboratory of Oilseeds processing,Ministry of Agriculture and Rural Affairs(202003)the Doctoral Research Startup Fund of Hubei University of Technology(BSQD2017027)。
文摘Achieving the reuse of traditional egg by-products,salted duck egg whites(SEW),is an urgent problem to be solved.In this current work,we constructed a heat-induced gel-assisted desalination method for SEW.Subsequently,a top-down way was utilized to prepare desalted duck egg protein nanogels(DEPN)with uniformly distributed diameters and their application in the oil/water(O/W)interface system was explored.The results revealed that the increase of DEPN concentration could lower the droplet size,however,the size was negatively correlated with the oil phase fraction.Moreover,the effect of pH,ionic strength,and temperature on the emulsion stability demonstrated that the DEPN-stabilized emulsion displayed superior physical stability under different conditions.The addition of NaCl resulted in the significant decrease in droplet size of the emulsion,while further increasing the NaCl concentration,the droplet size did not decrease accordingly.Besides,heat-treatment and cold-treatment had little negative effect on the stability of the emulsion.Even if the droplet size of the emulsion increased at 80℃for 3 h,the morphology of the emulsion remained unchanged.Our study demonstrated DEPN had great potential as a stabilizer for food-grade Pickering emulsions.
基金Supported by the Shanghai Municipal Commission for Special Project of Nanometer Science and Technology (Grant No. 0452nm068)
文摘One-pot synthesis of magnetic nanogels via photochemical method is reported in this paper. Poly(2-hydroxyethyl methacrylate)(PHEMA) magnetic nanogels are synthesized by in-situ polymeriza-tion of 2-hydroxyethyl methacrylate(HEMA) and N,N'-methylene-bis-(acrylamide)(MBA) in Fe3O4 aqueous suspension under UV irradiation. The structure and compositions of magnetic nanogels are characterized by FTIR,TGA,SEM,TEM and PCS. TGA measurement indicates that magnetic nanogels contain 90% magnetite. Both naked Fe3O4 and magnetic nanogels are superparamagnatic at room temperature according to magnetization curves. The swollen capability of the hydrogel shell is proved by contrasting the particles sizes obtained by SEM,TEM and PCS. Particle diameters can be manipu-lated by changing monomer concentration and irradiation time. A mechanism of the coating process is proposed.
基金The authors acknowledge the financial support of the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 713482(ALERT Cofound)and the China Scholarship Council(CSC,G.Z no.201706890012).
文摘The implementation of nanotechnology to develop efficient antimicrobial systems has a significant impact on the prospects of the biomedical field.Nanogels are soft polymeric particles with an internally cross-linked structure,which behave as hydrogels and can be reversibly hydrated/dehydrated(swollen/shrunken)by the dispersing solvent and external stimuli.Their excellent properties,such as biocompatibility,colloidal stability,high water content,desirable mechanical properties,tunable chemical functionalities,and interior gel-like network for the incorporation of biomolecules,make them fascinating in the field of biological/biomedical applications.In this review,various approaches will be discussed and compared to the newly developed nanogel technology in terms of efficiency and applicability for determining their potential role in combating infections in the biomedical area including implant-associated infections.
基金Supported by the Natural Science Foundation of Shandong Province (Grant No. Q2006F01)Scientific and Technological Project of Shandong Province (Grant No. 2007GG3WZ02066)+1 种基金Scientific and Technological Project of Department of Education, Shandong (Grant No. J07WC01)supported by the Key Laboratory of Bio-physics of Shandong Province
文摘One-pot synthesis of magnetic nanogels with excellent biocompatibility via the photochemical method is reported in this paper.Poly(PEGMA) modified superparamagnetic nanogels(poly(PEGMA) magnetic nanogels) were synthesized by in-situ polymerization using poly(ethylene glycol) methacrylate(PEGMA) as the monomer and N,N'-methylene-bis-(acrylamide)(MBA) as the cross-linking agent in magnetite aqueous suspension under UV irradiation.The surface functional groups and components of magnetic nanogels were analyzed by Fourier transform infrared spectroscopy(FTIR) and a thermogra-vimetric analyzer(TGA).The results indicated that the poly(PEGMA) magnetic nanogels were synthe-sized successfully by coating poly(PEGMA) on the Fe3O4 nanoparticles under UV irradiation,and the Fe3O4 nanoparticles content in this nanogels was above 50 wt%.The morphology,size,zeta-potential and magnetic property were also characterized.The magnetic nanogels had a nearly spherical shape and core-shell structure,the average size in aqueous system measured by photon correlation spec-troscopy(PCS) was 68.4 nm,which was much bigger than that in the dry state,the nanogels behaved superparamagnetically with saturated magnetization of 58.6 emu/g,and the zeta-potential was-16.3-_17.3 mV at physiological pH(6.8-7.4) which could help to maintain stability in blood.The preliminary application as drug carrier was made and the doxorubicin-loaded magnetic nanogels had an excellent property in slow-release.The experiment indicated that the magnetic nanogel was an ideal candidate carrier in target drug delivery systems and other biomedical application.
文摘Nanogels (NGs) as soft nanosized materials have gained a variety of interests in biomedical fields. The versatile NG scaffolds with 3-dimensional spherical shape, high loading efficiency, tunable surface functionalization, and excellent biocompatibility afford their uses as carrier to load mono- or multi-mode molecular imaging contrast agents (CAs). This review summarizes the synthesis routes and applications of NGs as CAs for molecular imaging applications including magnetic resonance (MR), computed tomography (CT), radionuclide, optical, and dual/mul- ti-modality imaging.
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505),DFG(SFB 985,Functional Microgels and Microgel Systems),National Natural Science Foundation of China(81801704 and 81761148028)Science and Technology Commission of Shanghai Municipality(18520750400)Shanghai Sailing Program(18YF1415300)。
文摘Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy.Here,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma.By an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization.After G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral core.Importantly,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo.As a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side effects.Remarkably,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake.Moreover,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug release.Encouragingly,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.
基金supported in part by a National Cancer Institute R01 award(CA182670,USA)a National Heart,Lung,and Blood Institute award(HL118498,USA).
文摘A novel photo-crosslinkable nanogel is prepared from a biodegradable polymer template with intrinsic photoluminescence and high photostability.The fluorescent nanogels display excellent biodegradability and cytocompatibility owed to the facile synthesis scheme involving a solvent-and surfactant-free onepot reaction,derived entirely from biocompatible monomers citric acid,maleic acid,L-cysteine,and poly(ethylene glycol).The resultant nanogels are less than 200 nm in diameter with a narrow size distribution and monodispersity,and demonstrate long-term structural stability in biological buffer for two weeks.To gauge potential in theranostic applications,the fluorescent nanogels were surface functionalized with biologically active RGD peptides and encapsulated with active anti-cancer drug Doxorubicin,resulting in a pH-responsive controlled drug release in acidic pH resembling tumor environments.The strong fluorescence of the nanogels enabled tracking of targeted drug delivery,showing that drug-loaded nanogels homed into the cytoplasmic regions of prostate cancer cells to significantly induce cell death.These photo-crosslinkable and biodegradable nanogels pose as a strong candidate for theranostic medicine,demonstrating versatile functionalization,high stability in biological buffers,and capacity for real-time fluorescence-based monitoring of targeted drug delivery.
基金the National Natural Science Foundation of China(Nos.12074348,U2004168,U1904142,and U21A2070)the China Postdoctoral Science Foundation(No.2020M682310)+1 种基金the Natural Science Foundation of Henan Province(No.212300410078)Science and Technology Department of Henan Province(No.182102410010).
文摘Carbon nanogels(CNGs)with dual ability of reactive oxygen species(ROS)imaging and photodynamic therapy have been designed with selfassembled chemiluminescent carbonized polymer dots(CPDs).With efficient deep-red/near-infrared chemiluminescence(CL)emission and distinctive photodynamic capacity,the H2O2-driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors,enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high-performance therapy for xenograft tumors.Mechanistically,ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2,enabling in vivo CL imaging.Meanwhile,part of the excited-state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen,endowing the apoptosis of tumor cells and thus enabling cancer therapy.These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents.
文摘In this study, a networked swellable dextrin nanogel (DNG) was developed to achieve stimulated responsive small interfering RNA (siRNA) release for melanoma tumor therapy, siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione- triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery.
基金This research was financially supported by the Sino-German Center for Research Promotion(GZ1505)National Natural Science Foundation of China(81801704 and 81761148028)+5 种基金the Science and Technology Commission of Shanghai Municipality(19XD1400100)Shanghai Sailing Program(18YF1415300)the China Scholarship Council(for X.Li)X.Shi also thanks the support by FCT-Fundaçao para a Ciencia e a Tecnologia through the CQM Base Fund-UIDB/00674/2020Programmatic Fund-UIDP/00674/2020by ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao,through the project M1420-01-0145-FEDER-000005-Centro de Química da Madeira-CQM+(Madeira 14-20 Program).
文摘For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.
基金supported by the National Natural Science Foundation of China(Grant No.U23A20591,52203201,52173149,and 81971174)the Youth Talents Promotion Project of Jilin Province(Grant No.202019)+1 种基金the Science and Technology Development Program of Jilin Province(Grant No.20210101114JC)Research Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin University(Grant No.KYXZ2022JC04).
文摘Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
基金the National Natural Science Foundation of China(Nos.21971161,21971160,and 21574078)Shanghai Pujiang Program(No.19PJ1403700)Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning.
文摘A series of thermoresponsive cationic dendronized copolymers and their corresponding nano gels containing den dritic oligoethylene glycol(OEG)units and guanidine groups were prepared,and their complexation,protect!on,and release of nucleic acids were investigated.The dendritic OEGs endow these copolymer materials with good biocompatibility and characteristic thermoresponsiveness,while cationic guanidine groups can efficiently bind with the nucleic acids.The dendritic topology also affords the copolymers specific shielding effect which plays an essential role in protecting the activity of nucleic acids.At room temperature,dendronized copolymers and the corresponding nanogels could efficiently capture and condense the nucleic acids,while above their cloud points(Tcps),more than 75%of siRNA could be released in 1 h triggered by ATP.More importantly,the copolymer showed protective capability to siRNA,while nano gels exhibit even better protection when compared to the copolymers due to the synergetic effect from the three-dimensional cross-linked network and high density of dendritic units in vicinity.This kind of smart dendr on ized copolymer nano gels form a no vel class of scaffolds as promisi ng materials for biomedical applicatio ns.
基金This work is financially supported by the National Natural Science Foundation of China(81400941,51473169).
文摘The urokinase-type plasminogen activator(uPA)loaded hollow nanogels(nUK)were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly(ethylene oxide).The resultant formulation is sensitive to diagnostic ultrasound(US)of 2 MHz.Herein,we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery(MCA).Via intravenous(i.v.)administration,the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation,leading to enhanced thrombolysis efficiency of the nUK,evidenced from smaller infarct volume and better clinical scores when compared to the i.v.dose of free uPA no matter with or without US intervention.Meanwhile,the preservation ability of the nanogels not only prolonged the circulation duration of the protein,but also resulted in the better blood-brain barrier protection of the nUK formulation,showing no increased risk on the hemorrhagic transformation than the controls.This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.
基金financially supported by the Chongqing Graduate Program of Research and Innovation (No. CYS21110)the National Natural Science Foundation of China (Nos. 51703187, 32071375)Chongqing Talents of Exceptional Young Talents Project, China (Nos. CQYC202005029 and cstc2021ycjh-bgzxm0061)
文摘Although targeted therapy and immunotherapy are now shining in the treatment of some cancers,chemotherapy is still the cornerstone of drug treatment for many cancer patients.The emergence of chemotherapy prodrugs can improve the drug activity and reduce the side effects of chemotherapy.When used,the tumor microenvironment has characteristics different from normal tissues,and the existence of the microenvironment provided a more convenient way to design responsive nanodrugs.Herein,we designed a glutathione(GSH)-responsive prodrug nanogels for enhancing tumor chemotherapy.In the nanogels of HHNP,10-hydroxycamptothecin(HCPT)played an essential role in killing cancer cells.HCPT was jointed with a cross-linker agent with disulfide bond and was further coated with polyethylene glycol,which not only prolonged the half-life of the drug,but also made HCPT accurate transport to the tumor fractions and achieved precise and controllable release.The proposal of HHNP effectively retained the biological activity of the drug,and introduced functions such as targeting,selective release and biodegradation,which greatly improved the medical efficiency of the drug and effectively reduced the toxic and side effects.This chemotherapeutic prodrug nanogel offers a new window for constructing efficient drug delivery platform.
基金supported by the 1000 Foreign Experts Program(no.WQ20163100341)the Shanghai Municipal Natural Science Foundation(nos.17ZR1440500 and 18490740100)d the Fundamental Research Funds for the Central Universities(no.222201714003).
文摘Nanogels hold promise as soft and functional carriers and nanoreactors,but whether they will ever reach the stage of large-scale application depends crucially on efficient production methods,and on what interesting properties and functionalities they can have.In particular,nanogels consisting of highly charged polyelectrolyte have not yet been very much explored.Here,the authors present a novel and generic strategy for controlled and efficient synthesis of a large diversity of polyelectrolyte nanogels.The method is based on polymerizing an ionic monomer in the presence of an oppositely charged polyion-neutral diblock copolymer as template,while adding a cross-linker.The growing polymer chains assemble with the template,forming polyion complex micelles,which dissociate upon increasing salt concentration.Subsequent separation yields nanogels with well-controlled size and properties,and free template polymers that can be used again.Our design can be applied generally to a wide range of both cationic and anionic monomers,as well as various cross-linkers.Scaled-up production presents no problems as increasing monomer concentration(hundreds of mM)and reaction volume(up to 1 L)hardly compromise product quality.Moreover,the obtained nanogels with their well-controlled size,morphology,chemistry,and cross-linking degree perform well as soft nanocarriers and catalytic nanoreactors.