Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

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.

Research Progress of Zhuang Medicine Combined with Nanogels in Mastitis

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.

Characterization and oil recovery enhancement by a polymeric nanogel combined with surfactant for sandstone reservoirs

The characterization and enhanced oil recovery mechanisms of a nanosized polymeric cross-linked gel are presented herein.A negatively charged nanogel was synthesized using a typical free radical suspension polymerization process by employing 2-acrylamido 2-methyl propane sulfonic acid monomer.The synthesized nanogel showed a narrow size distribution with one peak pointing to a predominant homogeneous droplet size.The charged nanogels were also able to adsorb at the oil-water interfaces to reduce interfacial tension and stabilize oil-in-water emulsions,which ultimately improved the recovered oil from hydrocarbon reservoirs.In addition,a fixed concentration of negatively charged surfactant(sodium dodecyl sulfate or SDS)was combined with different concentrations of the nanogel.The effect of the nanogels combined with surfactant on sandstone core plugs was examined by running a series of core flooding experiments using multiple flow patterns.The results show that combining nanogel and SDS was able to reduce the interfacial tension to a value of 6 Nm/m.The core flooding experiments suggest the ability of the nanogel,both alone and combined with SDS,to improve the oil recovery by a factor of 15%after initial seawater flooding.

Phase Transition of Poly（acrylic acid-co-N-isopropylacrylamide） Core-shell Nanogels

A series of poly（acrylic acid） macromolecular chain transfer agents with different molecular weights were synthesized by reversible addition-fragmentation chain transfer （RAFT） poly- merization and characterized by 1^H NMR and gel permeation chromatography. Multiresponsive core-shell nanogels were prepared by dispersion polymerization of N-isopropylacrylamide in water using these poly（potassium acrylate） macro-RAFT agents as the electrostcric stabilizer. The size of the nanogels decreases with the amount of the macro-RAFT agent, indicating that the surface area occupied by per polyelectrolyte group is a critical parameter for stabilizing the nanogels. The volume phase transition and the zeta potentials of the nanogels in aqueous solutions were studied by dynamic light scattering and zetasizer analyzer, respectively.

Fucoidan-Based Theranostic Nanogel for Enhancing Imaging and Photodynamic Therapy of Cancer

In this study, a fucoidan-based theranostic nanogel(CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker and photosensitizer is developed to achieve acti-vatable near-infrared fluorescence imaging of tumor sites and an enhanced photodynamic therapy(PDT) to induce the com-plete death of cancer cells. A CFN-gel has nanomolar a nity for P-selectin, which is overexpressed on the surface of tumor neovascular endothelial cells as well as many other cancer cells. Therefore, a CFN-gel can enhance tumor accumulation through P-selectin targeting and the enhanced permeation and retention e ect. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation-induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. Since a CFN-gel also shows nanomolar a nity for the vascular endothelial growth factor, it also provides a significant anti-tumor e ect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high e cacy and specificity.

Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin

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.

A New Type of Nanogel Carrier based on Mixed Pluronic Loaded with Low-Dose Antitumor Drugs

To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.

A novel nanogel delivery of poly-α,β-polyasparthydrazide by reverse microemulsion and its redox-responsive release of 5-Fluorouridine

To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.

Functional Capsules Encapsulating Molecular-Recognizable Nanogels for Facile Removal of Organic Micro-Pollutants from Water

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.

Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin

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.

A Programmable Hybrid DNA Nanogel for Enhanced Photodynamic Therapy of Hypoxic Glioma

Photodynamic therapy(PDT)is a promising cancer therapy due to the evident advantages of a rapid curative eff ect,minimal or non-invasiveness,and circumvention of drug resistance.However,the hydrophobicity of photosensitizers and the hypoxic tumor microenvironment in solid tumors reduce the therapeutic eff ect of PDT immensely.Herein,we construct a programmable hybrid mesoporous silica nanoparticle/DNA nanogel(H-DNA nanogel)for enhanced PDT.The H-DNA nanogel is constituted with a virus-like mesoporous silica nanoparticle(VMSN)as the core to provide an appropriate nano-interface and a self-assembly programmable DNA hydrogel layer based on rolling circle amplifi cation(RCA)as the shell.Two kinds of G-quadruplex structures inserted with a hemin and zinc phthalocyanine(ZnPc)photosensitizer are introduced into the H-DNA nanogel by base pairing.The two modules of G-quadruplex structure work as an oxygen supplement in the hypoxic tumor microenvironment and increase the yield of singlet oxygen,respectively.Our hybrid DNA nanogel system provides a modular platform for effi cient cancer PDT and has great potential in the broader biomedical fi eld.

Self-Assembled Dextrin Nanogel as Curcumin Delivery System

Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this study, we show that self-assembled nanogels obtained from hydrophobically modified dextrin are effective curcumin nanocarriers. The stability and loading efficiency of curcumin-loaded nanogel depends on the nanogel/curcumin ratio. Higher stability of the formulation is achieved in water than in PBS buffer, as evaluated by dynamic light scattering and fluorescence measurements. The in vitro release profile, using sink conditions, indicates that dextrin nanogel may perform as a suitable carrier for the controlled release of curcumin. Biological activity of curcumin-loaded nanogel in HeLa cell cultures was assessed using the MTS assay.

Conformationally Dynamic Supramolecular Single Chain Nanogels for Mutilscale Biomechanical Regulation of Stem Cells

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.

Desalted duck egg white nanogels as Pickering stabilizers for food-grade oil-in-water emulsion

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.

Radiation-Induced Synthesis of Polyvinylpyrrolidone （PVP） Nanogels

Nanogels-particles of polymer gels having the dimensions in the order of nanometers-are gaining attention for their wide application as biomaterials. Mainly, the nanogels are promising novel pharmaceutical carriers for small biologically active agents, bin macromolecules and can be chemically modified to incorporate various ligands for targeted drug delivery. This important factor has stimulated research on dissimilar science field such as nanotechnology and biotechnology, polymer and materials sciences, biochemistry, radiation chemistry and pharmaceutical sciences. A multitude of techniques have been described for the synthesis of this nanomaterial from polymers. However, the use of ionizing radiation （γ, e-） has demonstrated to be especially suitable for obtaining polymeric nanogels with a high degree of purity for biomedical applications, although the gamma radiation has not been widely utilized for these purposes. The aim of this paper is to develop the synthesis of PVP （polyvynilpyrrolidone） nanogels by gamma irradiation, for their evaluation as potential pharmaceutical carriers. Experiments were performed using argon saturated solution of PVP （0.1-1%）. Crosstinking reactions were carried out in a gamma irradiation chamber with a 60Co source （ISOGAMMA LLCo）, at room temperature. The PVP concentration influence was evaluated in PVP solutions （0.1% and 0.25%） at 15 kGy. The SEM （scanning electron microscopy）, ATR （attenuate total reflection spectroscopy）, DLS （dynamic light scattering）, and viscosimetry were used as characterization techniques.

^(188)Re labeled MPEG-modified superparamagnetic nanogels: preparation and preliminary application in mice

Superparamagnetic poly(acrylamide) magnetic nanogels produced via photochemical method have been developed. After Hoffmann degradation of carbonyl, the nanogels with amino groups, or poly(acrylamide-vinyl amine) magnetic nanogels, were also obtained. And the magnetic nanogels were further modified by methoxy poly(ethylene glycol) (MPEG) for higher dispersibility and stability. The MPEG-modified magnetic nanogels were characterized by X-ray diffraction (XRD), photo correlation spectroscopy (PCS) and scanning electron microscopy (SEM), respectively. The MPEG-modified magnetic nanogels were labeled by 188Re radiopharmaceuticals and intra-venously injected into tails of mice in the presence and absence of a 0.5 T external magnetic field targeted on the bel-lies. The radioactivity distribution was monitored in vivo. In the absence of magnetic field, the radioactivity was mainly distributed in liver, spleen, kidney, stomach and lung. In the presence of the magnetic field, the radioactivity was mainly accumulated on the targeted point, verifying the magnetically targeted character.

ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape

In the field of cancer therapy,inhibiting autophagy has emerged as a promising strategy.However,pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1(PD-L1),enabling tumor immune evasion.To address this issue,we developed innovative ROS-responsive cationic poly(ethylene imine)(PEI)nanogels using selenol chemistry-mediated multicomponent reaction(MCR)technology.This procedure involved simple mixing of low-molecular-weight PEI(LMW PEI),γ-selenobutylacetone(γ-SBL),and poly(ethylene glycol)methacrylate(PEGMA).Through high-throughput screening,we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels,which exhibited a size of approximately 200 nm,excellent colloidal stability,and the most effective PD-L1 silencing efficacy.These nanogels demonstrated enhanced uptake by tumor cells,excellent oxidative degradation ability,and inhibited autophagy by alkalinizing lysosomes.The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I(MHC-I),resulting in robust proliferation of specific CD8+T cells and a decrease in MC38 tumor growth.As a result,the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy,upregulation of MHC-I,and downregulation of PD-L1.Designed with dynamic diselenide bonds,the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

In-situ synthesis of PHEMA magnetic nanogels via photochemical method

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.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.