Preparation and characterization of pH-responsive metal-polyphenol structure coated nanoparticles

In this paper,tannic acid(TA)and Fe~(3+)were added to form a layer of metal-polyphenol network structure on the surface of the nanoparticles which were fabricated by zein and carbon quantum dots(CQDs)encapsulating phlorotannins(PTN).pH-Responsive nanoparticles were prepared successfully(zein-PTN-CQDs-Fe-~Ⅲ).Further,the formation of composite nanoparticles was confirmed by a series of characterization methods.The zeta-potential and Fourier transform infrared spectroscopy data proved that electrostatic interaction and hydrogen bonding are dominant forces to form nanoparticles.The encapsulation efficiency(EE)revealed that metal-polyphenol network structure could improve the EE of PTN.Thermogravimetric analysis and differential scanning calorimetry experiment indicated the thermal stability of zein-PTN-CQDs-Fe~Ⅲnanoparticles increased because of metal-polyphenol network structure.The pH-responsive nanoparticles greatly increased the release rate of active substances and achieved targeted release.

Pharmacokinetics of a ternary conjugate based pH-responsive 10-HCPT prodrug nano-micelle delivery system

A pH-responsive conjugate based 10-hydroxycamptothecin-thiosemicarbazide-polyethene glycol 2000 (10-HCPT-hydro-PEG) nano-micelles were prepared in our previous study. In the present study, ultra-performance liquid chromatography (UPLC-MS) method is developed to investigate its pharmacokinetics and biodistribution in tumor bearing mice. The results demonstrated that the conjugate circulated for a much longer time in the blood circulation system than commercial 10-HCPT injection, and bioavailability was significantly improved compared with 10-HCPT. In vivo biodistribution study showed that the conjugate could enhance the targeting and residence time in tumor site.

CaCO3-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy

Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.

Towards recycling purpose:Converting PET plastic waste back to terephthalic acid using pH-responsive phase transfer catalyst

Converting polyethylene terephthalate(PET)wastes to its monomer and valuable chemicals via ecofriendly chemical method is still a challenge task.Previously,phase transfer catalysts used for alkaline hydrolysis were soluble in reaction media and hardly separated after reaction.Here,we reported several pH-responsive catalysts combined alkyl quaternary ammonium units with heteropolyacid anion for achieving stepwise product/catalyst separation and catalyst recycling.The properties of homogeneous/heterogeneous transfer behavior allow catalyst to be easily separated from reaction media by adjusting of pH value.Among them,[C_(16)H_(33)N(CH_(3))_(3)]_(3)PW_(12)O_(40)(abbreviated as[CTA]_(3)PW)exhibits the highest activity and the most suitable pH responsive values.Such a pH triggered switchable catalytic system not only shows good performance for depolymerization of pure PET,but also some real PET wastes such as coloured trays and PE/PET complex films could be completely degraded into terephthalic acid.Additionally,the reaction kinetics and activation energy of PET alkaline hydrolysis also studied with and without pH-responsive[CTA]_(3)PW.

Preparation of Hollow-Porous Rosin-Based Polyurethane Microspheres with pH-Responsive Characteristics

Preparation of polymer microspheres from naturally occurring resource is a challenge.Here,a rosin-based polyol(RAG)was used to prepare polyurethane resin(RPU)firstly,and then act as both self-assembled precursor and emulsifier,rosin based polyurethane microspheres(RPUMs)were prepared.In the process of self-emulsification,the RPU formed vesicles by self-assembly.The outer shell of the vesicle consisted of hydrophilic segments,while the inner shell contained the hydrophobic phase.After cross-linking the RPU and removal of the solvent in the core,the porous-hollow microspheres with pH-sensitive were obtained.The microspheres were characterized by optical microscope(OM),scanning electron microscopy(SEM)and transmission electron microscope(TEM).The effect of type and amount of the hydrophilic chain extender,and solvent on the morphology,particle size and distribution,and buffer volume of the microspheres were determined.The best conditions for synthetic RPUMs were as follows:n_(NCO)/n_(OH)=1,n_(RAG):n_(1-(2-hydroxyethyl)piperazine)=4:6,with azodiisobutyronitrile level of 1.0 wt.%,based on reactive monomers,mixing speed of both emulsification and polymerization at 400 r·min-1,the RPUMs synthesized had porous-hollow structure with a buffer volume of 1.6 mL.

Ultrasmall pH-responsive silicon phthalocyanine micelle for selective photodynamic therapy against tumo

Targeted photodynamic therapy(TPDT)based on the photosensitizers responsive for tumor micr oenvironment is promising because of the better anti-tumor effect and less phototoxicity against normal tissue than the traditional PDT.Nanoparticle based stimuli responsive photo-sensitizers have been widely explored for TPDT.Based on the acidic microenvironments in solid tumors,an ultrasmall pH-responsive silicon phthalocyanine nanomicelle(PSN)(smaller than 10 nm)was designed for selective PDT of tumor.PSN had high drug loading efficacy(more than 28%)and exhibited morphological transitions,enhanced fuorescence and improved singlet∞x-ygen yield under acidic environments.PSN was renal dlearable and could rapidly accumulate and be retained at tumor sites,achieving a tumor-inhibiting ffect better than phthalocyanine micelle without pH response.Tumors of mice treated with PSN for PDT were completely ablated without recurrence.Thus,we have developed a phthalocyanine-based pH responsive micelle with excellent tumor targeting ability,which is expected to realize the selective PDT of tumor.

Preparation and Properties of pH-Responsive Intelligent Medical Dressing Based on Bacterial Cellulose/Polyacrylic Acid

Bacterial cellulose/polyacrylic acid (BC/PAA) pH-responsive hydrogels were prepared by free-radical polymerization (in situ) using BC as the raw material and AA as the monomer. The hydrogels were loaded with curcumin (Cur) to prepare pH-responsive intelligent medical dressings. The preparation process of the hydrogels was optimized by a single factor and response surface experiment using their swelling degree as an index. The structures of BC/PAA pH-responsive hydrogels were characterized by scanning electron microscope (SEM), Fourier Transform Infrared spectrometer (FTIR), X-ray diffraction (XRD), and tensile tester, and the swelling properties, mechanical properties, bacteriostatic properties, and drug release behavior were investigated. The results showed that the BC/PAA pH-responsive hydrogel has a three-dimensional network structure with the swelling rate up to 1600 g/g, compressive strength of up to 8 KPa, and good mechanical properties, and the drug release behavior was in line with the logistic dynamics model, and it has good inhibitory effects on common pathogens of wound infection: E. coli, S. aureus, and P. aeruginosa.

MOF-based magnetic microrobot swarms for pH-responsive targeted drug delivery

Metal-organic frameworks(MOFs)hold significant potential as vehicles for drug delivery due to their expansive specific surface area,biocompatibility,and versatile attributes.Concurrently,magnetically actuated micro/nano-robots(MNRs)offer distinct advantages,such as untethered and precise manipulation.The fusion of these technologies presents a promising avenue for achieving non-invasive targeted drug delivery.Here,we report a MOF-based magnetic microrobot swarm(MMRS)for targeted therapy.Our approach overcomes limitations associated with a single MNR,including limited drug loading and the risk of loss during manipulation.We select Zeolitic Imidazolate Framework-8(ZIF-8)as the drug vehicle for its superior loading potential and p H-sensitive decomposition.Our design incorporates magnetic responsive components into the one-pot synthesis of Fe@ZIF-8,enabling collective behaviors under actuation.Tuning the yaw angle of alternating magnetic fields and nanoparticles'amount,the MMRSs with controllable size achieve instantaneous transformation among different configurations,including vortex-like swarms,chain-like swarms,and elliptical swarms,facilitating adaptation to environmental variations.Transported to the subcutaneous T24 tumor site,the MMRSs with encapsulated doxorubicin(DOX)automatically degrade and release the drug,leading to a dramatic reduction of the tumor in vivo.Our investigation signifies a significant advancement in the integration of biodegradable MOFs into microrobot swarms,ushering in new avenues for accurate and non-invasive targeted drug delivery.

Carbon dots-enhanced pH-responsive lubricating hydrogel based on reversible dynamic covalent bondings

Due to the various pH liquid environment in nature,the pH-responsive lubricating hydrogel is widely investigated and developed for tissue interface substitute.However,the applied liquid environment will lead to poor mechanical property and weaken the pH-responsive capability.In this work,a carbon dotsenhanced pH-responsive lubricating hydrogel is developed by combining a pH-responsive section of dynamic PVA-borax network into a PAAm covalent polymer network.The formed hydrogel presents a partial gel-sol transition under controlled pH environments.At low pH environments(<6.0),the formed lubricating layer originated from dynamic disassembly of PVA-borax hydrogel,and brings the lubricating properties on the hydrogel surface.Moreover,the mechanical strength and lubrication properties are well promoted by introducing the carbon dots into the hydrogel,the blue sol layer can be observed more visually under the fluorescence microscope.The pH-response also exhibits well reversibility.The prepared hydrogel broadens the idea for designing pH-responsive soft materials for soft lubricating actuator or robot.

Manganese-Zeolitic Imidazolate Frameworks-90 with High Blood Circulation Stability for MRI-Guided Tumor Therapy

Zeolitic imidazolate frameworks(ZIFs)as smart drug delivery systems with microenvironment-triggered release have attracted much attention for tumor therapy.However,the exploration of ZIFs in biomedicine still encounters many issues,such as inconvenient surface modification,fast drug release during blood circulation,undesired damage to major organs,and severe in vivo toxicity.To address the above issues,we developed an Mn-ZIF-90 nanosystem functionalized with an originally designed active-targeting and pH-responsive magnetic resonance imaging(MRI)Y1 receptor ligand[Asn28,Pro30,Trp32]-NPY(25-36)for imaging-guided tumor therapy.After Y1 receptor ligand modification,the Mn-ZIF-90 nanosystem exhibited high drug loading,better blood circulation stability,and dual breast cancer cell membrane and mitochondria targetability,further favoring specific microenvironment-triggered tumor therapy.Meanwhile,this nanosystem showed promising T1-weighted magnetic resonance imaging contrast in vivo in the tumor sites.Especially,this nanosystem with fast clean-up had almost no obvious toxicity and no damage occurred to the major organs in mice.Therefore,this nanosystem shows potential for use in imaging-guided tumor therapy.

Chitosan nanoparticles crosslinked by glycidoxypropyltrimethoxysilane for pH triggered release of protein

pH-responsive-chitosan nanoparticles for the control release of protein drug were prepared by combining two-step crosslinking method, in which chitosan was subsequently crosslinked by sodium tripolyphosphate （TPP） and glycidoxypropyltrimethoxysilane （GPTMS）. Compared with TPP crosslinked chitosan particles, the two-step crosslinked nanoparticles were not only pH-responsive but also more stable in wide pH range. Fluorescein isothiocyanate （FITC） labeled anti-human-IgG antibody was used as a model protein drug for evaluating the control release profile of the nano-carrier. The amount of released antibody increased from 5.6% to 50% when the pH of solution shifted from 7.4 to 6.0. The results suggest the possible application of the nanoparticles as pH- responsive drug delivery materials.

Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment

To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site.After that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.

Hollow MnO_2/GNPs serving as a multiresponsive nanocarrier for controlled drug release

In this work,hollow manganese dioxide/gold nanoparticle(MnO2/GNPs)hybrid drug nanocarriers were prepared by coupling the gold nanoparticles(GNPs)with hollow structure manganese dioxide(MnO2).Among them,GNPs have been used as near-infrared(NIR)-responsive element for photothermal effect under NIR laser irradiation.The glutathione(GSH)-responsive and p H-responsive performances of drug release were derived from hollow MnO2.Particularly,Doxorubicin hydrochloride(DOX)can be loaded into hollow MnO2/GNPs with the drug loading efficiency up to 82.0%.Moreover,the photothermal effect and GSH-/pH-responsive properties of hollow MnO2/GNPs were investigated.The hollow MnO2/GNPs possessed satisfactory drug release efficiency(ca.87.4%of loaded drug released in 12 h)and have high photothermal conversion efficiency,multiresponsive properties,and degradability.Finally,the kinetics of drug release was discussed in detail.Thus,our finding highlights that the multiresponsive nanocarriers are of great potential in the field of drug controlled release.

Antibacterial hydrogel with pH-responsive microcarriers of slow-release VEGF for bacterial infected wounds repair

Bacterial infection causes wound inflammation and makes angiogenesis difficult.It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing.The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor(VEGF)that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release.The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles(AgNPs)in situ,and dynamically crosslink with the polyacrylamide,which forms a stable slow-release system with different release behavior for the VEGF and AgNPs.The hydrogel inhib-ited bacterial formation and accelerated wound healing.With the hydrogel dressing,83.3%±4.29%of the wound heals at day 7,which is 40.9%±8.5%higher than the non-treatment group in defect infected model.The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines,and the release of VEGF in the middle and late phases of wound healing in response to pH changes pro-motes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine.The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microen-vironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases.Collectively,the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.

Ion Recognition and Analytical Application of a Fibroin Modified Electrode

A novel fibroin modified electrode with ion recognition was reported. The membranewith isoelectric point of pH 4.5, was modified on graphite and carbon fiber electrodes. ThepH-responsive ion recognition of the modified electrode was investigated by use of someneurocompounds. The fibroin carbon fiber electrode has been used for in-vivo determination.

Effect of Polysaccharide Species on Storage Stability of Alginate Capsules Containing <i>α</i>-Tocopherol

Alginate capsules containing α-tocopherol were prepared adding polysaccharide species such as κ-carrageenan, gellan gum, pectin, curdlan and ghatti gum. The effects of polysaccharide species and the diameters of α-tocopherol on storage stability of the capsules were investigated and characterized in detail. As the contact angle of α-tocopherol to the capsule shell strongly affected storage stability, the contact angle was measured on the model sheet made of calcium alginate with polysaccharide species. The leakage ratio decreased with the contact angle and increased with the diameter of α-tocopherol. The capsules made of calcium alginate with gellan gum showed the largest contact angle and the highest storage stability. The capsules made of calcium alginate with curdlan, ghatti gum and pectin were harder than other capsules and showed higher storage stability. All the capsules showed the almost similar swelling ratio in the acidic solution with pH 4, but showed the different swelling ratios according to the polysaccharide species in the alkali solution with pH 9. The tablets were prepared with the wet and the dried capsules. The tablets prepared with the dried capsules showed higher storage stability.

Antimicrobial hydrogel with multiple pH-responsiveness for infected burn wound healing

Burns are a common medical problem globally,and wound infection is one of the major causes of inducing related complications.Although antibiotics effectively prevent wound infections,the misuse of antibiotics has created a new problem of superbugs.Herein,we propose a new strategy to obtain pH-responsive antimicrobial P-ZIF(ZIF:zeolitic imidazolate framework)by loading polyhexamethylenebiguanide(PHMB)into the framework of ZIF-8 nanoparticles.This will enable PHMB to be released in the weak acid environment of an infected wound.To address burn infections,P-ZIF nanoparticles were loaded into a hydrogel system made of sodium alginate(SA)and 3-aminophenylboronic acid modified human-like collagen(H-A)through borate ester bonds.The resulting H-A/SA/P-ZIF(HASPZ)hydrogel dressing not only possesses antibacterial and wound healing properties but also has dual pH responsiveness to prevent the overuse of medication while effectively treat deep second-degree burns.Therefore,P-ZIF nanoparticles and the corresponding HASPZ hydrogel dressing are considered of significant importance in antimicrobial,drug delivery,and wound repair.

Facile Fabrication of Hyperbranched Polyacetal Quaternary Ammonium with pH-Responsive Curcumin Release for Synergistic Antibacterial Activity

In the current global crisis of antibiotic resistance,persuit of an effective multi-pathway collaborative approach to enhance antibacterial activity is urgently needed.Here,a kind of hyperbranched polyacetal quaternary ammonium(Hyper-ace-QA)with efficiently antibacterial function were synthesized by a succession of efficient click strategies.The high molecular weights can be obtained just after UV irradiation for 3 h,and the grafting ratio can be easily adjusted through controlling solvent system,molar ratio,and temperature.Cytotoxicity studies indicated that Hyper-ace-QA had good biocompatibility and can be used as a potential antibacterial dressing.More importantly,after in situ encapsulation of bioactive curcumin drugs into the hyperbranched intramolecular cavities,the acid-liable acetal linkers within the hyperbranched backbone made the loading antibacterial drugs rapidly release with pH-or bacterial-responsive behaviors since many bacteria can produce acids at the infection site by the combined actions of immune response and bacterial metabolism.Therefore,the integration of quaternary ammonium characteristics and pH-triggered curcumin release could facilitate the antibacterial activity against gram-positive Staphylococcus aureus.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be promising therapeutic alternatives for first aid treatment of wound infection in critical situations.

A soluble pH-responsive host-guest-based nanosystem for homogeneous exosomes capture with high-efficiency

Exosomes offer ideal biomarkers for liquid biopsies.However,high-efficient capture of exosomes has been proven to be extreme challenging.Here,we report a soluble pH-responsive host-guest-based nanosystem(pH-HGN)for homogeneous isolation of exosomes around physiological pH.The pH-HGN consists of two specifically functionalized modules.First,a pH-responsive module,poly-dimethylaminoethyl methacrylate,provides homogeneous capture circumstances and sharp pH-triggered self-assembly separation in aqueous solution to improve capture efficiency and reduce nonspecific adsorption.Second,a host-guest module,poly-acrylamide azobenzene andβ-cyclodextrin linked with exosomes-specific antibody,could act as the"cleavable bridge"to specific capture and subsequent rapid release of captured exosomes through host-guest interaction betweenβ-cyclodextrin and AAAB moieties.The pH-HGN offered high capture efficiencies for exosomes from two different cell lines,which were 90.2%±0.28%and 87.0%±4.6%for H1299 and MCF-7 cell-derived exosomes,respectively.The purity of isolated exosomes was(1.49±0.71)×10^(11)particles/μg,which was 4.1 times higher compared with the gold standard ultracentrifugation(UC)method.Furthermore,the isolated exosomes via the pH-HGN can preserve well integrity and biological activity.The developed pH-HGN was further successfully applied to differentiate lung cancer patients from healthy persons.These findings indicated that pH-HGN is a promising strategy in exosomes-based research and downstream applications.

High-sensitivity intelligent packaging films harnessing rose anthocyanins and hydrophilic silica aerogel for visual food freshness monitoring

The enhancement of the sensitivity for anthocyanin-based indicator films in food freshness monitoring in real time is important for application.In this study,hydrophilic silica aerogel(SiO2 NA)was incorporated into corn starch(CS)/chitosan(CH)/rose anthocyanins(RACNs)-encapsulated potato amylopectin nanoparticles(APNPs)composite film to increase the sensitivity for shrimp freshness detection.The microstructure of films revealed that the gas absorption capacity was improved by amorphous SiO2 NA via hydrogen interactions.The pore size(1.74–5.60 times),pore volume(3.92–5.60 times),and specific surface area(2.21–2.34 times)of films increased with the addition of SiO2 NA.The sensing of NH3 and pH and the reversibility of films were also reinforced.Meanwhile,the pH-responsive films containing SiO2 NA changed visibly in color from purple–red to orange–gray and finally to gray,enabling effective monitoring of shrimp freshness during storage at 4°C.Thus,anthocyanin-based indicator films with improved sensitivity by adding SiO2 NA were successfully designed for monitoring shrimp freshness.