Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we ha...Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we have developed a novel charge-reversible nanogel to deliver paclitaxel(PTX)dimers(DPP)with enhanced stability and targeting precision.The nanogels exhibit a dynamic charge-reversal mechanism responsive to the acidic tumor microenvironment(TME),optimizing the cellular uptake of prodrugs.In the high glutathione(GSH)conditions within cancer cells,the disulfide bonds in the DPP are cleaved,resulting in the intracellular release of active PTX and reduced drug toxicity to normal cells.In vivo pharmacokinetic studies revealed an extended plasma elimination half-life for the charge-reversible nanocarriers,and antitumor efficacy studies demonstrated superior tumor suppression with minimal systemic toxicity.This research underscores the potential of integrating charge-reversal and responsive release mechanisms into one nanocarrier system,balancing the long circulation and high tumor cell internalization capacity of the nanocarrier,and providing a promising strategy for targeted delivery of nanomedicine.展开更多
Reactive oxygen species(ROS)-mediated anticancer modalities,which disturb the redox balance of cancer cells through multi-pathway simulations,hold great promise for effective cancer management.Among these,cooperative ...Reactive oxygen species(ROS)-mediated anticancer modalities,which disturb the redox balance of cancer cells through multi-pathway simulations,hold great promise for effective cancer management.Among these,cooperative physical and biochemical activation strategies have attracted increasing attention because of their spatiotemporal controllability,low toxicity,and high therapeutic efficacy.Herein,we demonstrate a nanogel complex as a multilevel ROS-producing system by integrating chloroperoxidase(CPO)into gold nanorod(AuNR)-based nanogels(ANGs)for cascade-amplifying photothermal-enzymatic synergistic tumor therapy.Benefiting from photothermal-induced hyperthermia upon near-infrared(NIR)laser exposure,the exogenous ROS(including H2O2)were boosted by the AuNR nanogel owing to the intercellular stress response.This ultimately promoted the efficient enzyme-catalyzed reaction of loaded CPO combined with the rich endogenous H2O2 in tumor cells to significantly elevate intracellular ROS levels above the threshold for improved therapeutic outcomes.Both in vitro and in vivo studies have verified the cascade-amplifying ROS-mediated antitumor effects,providing feasible multimodal synergistic tactics for tumor treatment.展开更多
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–vip 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-vip 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-vip 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 vip 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-vip 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
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
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
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 fo...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.展开更多
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 b...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.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
The present paper develops the scaling theory of polyelectrolyte nanogels in dilute and semidilute solutions. The dependencies of the nanogel dimension on branching topology, charge fraction, subchain length, segment ...The present paper develops the scaling theory of polyelectrolyte nanogels in dilute and semidilute solutions. The dependencies of the nanogel dimension on branching topology, charge fraction, subchain length, segment number, solution concentration are obtained. For a single polyeleetrolyte nanogel in salt free solution, the nanogel may be swelled by the Coulombie repulsion （the so-called polyelectrolyte regime） or the osmotic eounterion pressure （the so-called osmotic regime）. Characteristics and boundaries between different regimes of a single polyelectrolyte nanogel are summarized. In dilute solution, the nanogels in polyeleetrolyte regime will distribute orderly with the increase of concentration. While the nanogels in osmotic regime will always distribute randomly. Different concentration dependencies of the size of a nanogel in polyeleetrolyte regime and in osmotic regime are also explored.展开更多
Developing multifunctional nanoplatforms capable of addressing the excessive oxidative stress and cytokine storm in inflammatory diseases remains a challenging task.Herein,we report the construction of stimuli-respons...Developing multifunctional nanoplatforms capable of addressing the excessive oxidative stress and cytokine storm in inflammatory diseases remains a challenging task.Herein,we report the construction of stimuli-responsive nanogels(NGs)through a reverse microemulsion method utilizing taxifolin(Tax)-functionalized generation 3 poly(amidoamine)dendrimers as a monomer and diselenide compound as a crosslinker.Subsequently,exosomes derived from mesenchymal stem cells(MSC-Exos)were coated on the surface of the NGs.The formed multifunctional biomimetic NGs(MSC@DT-NGs)with an average size of 78.3 nm exhibit good colloidal stability and hydrogen peroxide/pH-dual responsive drug release behavior.Meanwhile,the MSCExo coating affords the NGs with excellent macrophage targeting ability to enter the target cells via the clathrin-mediated endocytosis pathway,effectively alleviating intracellular excessive oxidative stress and balancing the antioxidant system through the incorporated anti-oxidant Tax.Furthermore,the MSC@DT-NGs polarize activated macrophages towards the anti-inflammatory M2 phenotype and quell the cytokine storm by inhibiting the intracellular nuclear factor-kappa B signaling pathway.Notably,the MSC@DT-NGs effectively repair lung injury and alleviate acute lung injury(ALI)symptoms by controlling pulmonary inflammation,reducing oxidative stress levels,as well as inhibiting neutrophil infiltration as demonstrated by an ALI mouse model.This study presents an innovative dual-responsive biomimetic nanoplatform that integrates Tax and MSC-Exos for targeted antioxidant delivery and immunomodulation,providing a translational strategy for treating inflammatory disorders.展开更多
To date,more biodegradable polymers have been developed due to the growing recognition of the advantages of biodegradable and biocompatible polymers for biomedical applications.In this study,we introduce the synthesis...To date,more biodegradable polymers have been developed due to the growing recognition of the advantages of biodegradable and biocompatible polymers for biomedical applications.In this study,we introduce the synthesis and characterization of innovative polymers that incorporate biodegradable backbones composed of trimethylol-propane and adipic acid moieties and biocleavable side chains containing pyridyl disulfide groups.Notably,their synthesis is straightforward and catalyst-free under ambient conditions,minimizing potential toxicity and immune responses caused by catalyst residues in polymer materials.The new polymers have desired molecular weight(Mn:18.8 kDa)with a narrow dispersion(PDI:1.32)and offer complete biodegradability,biocompatibility,crosslinking capabilities,and opportunities for covalent chemical modifications.These features make them particularly suitable for use in biomedical materials and devices.Additionally,due to their unique properties,these polymers have been successfully formulated into polymeric gels and nanogels,which are biodegradable as well.Using a near-infrared fluorescent probe as a model cargo,we demonstrated the creation of a biosafe and sustainable nanogel system for agent delivery,with an average size of approximately 70 nm.In these nanogels,agent molecules are covalently attached to the scaffold,thereby avoiding uncontrolled premature release and burst release in the bloodstream and mitigating associated systemic toxicity and side effects.The nanogels can also be easily functionalized with targeting ligands for disease-specific delivery.These polymers induced minimal toxicity toward human cells and displayed excellent in vivo biocompatibility,highlighting the significant potential of their polymeric gels and nanogels for a broad spectrum of biomedical applications.展开更多
Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To ...Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To address this;we propose a smart nanoplatform(P@BAO-DOX)for synergistic chemo-photodynamic therapy;featuring efficient PDT;controllable drug release;and fluorescence imaging guidance.We designed an aggregation-induced emission(AIE)-based PS(BAO)with effective ROS generation and NIR-II fluorescence.Additionally;BAO as a PS and doxorubicin(DOX)as a chemo drug were encapsulated in p H-responsive nanogels(PNA)to obtain P@BAO-DOX nanogels.Upon uptake by tumor cells;the nanogel releases drugs in acidic conditions;leading to cell death.White light irradiation further triggers BAO to produce substantial ROS;enhancing phototoxicity and synergistic chemo-PDT cancer therapy.Thus;P@BAO-DOX nanogels;as a smart nanoplatform;offer precise drug release and efficient ROS generation for imaging-guided chemo-PDT synergistic therapy;showing promise in advancing cancer treatment.展开更多
Chimeric antigen receptor T-cells(CAR-T)therapy has demonstrated significant anti-tumor responses in hematological malignancies and even solid tumors.However,the overactivation of CAR-T cells in vivo can lead to cytok...Chimeric antigen receptor T-cells(CAR-T)therapy has demonstrated significant anti-tumor responses in hematological malignancies and even solid tumors.However,the overactivation of CAR-T cells in vivo can lead to cytokine release syndrome(CRS),with the unpredictable timing and severity of its onset making it difficult to manage effectively.In this study,a strategy was proposed to prevent and treat CAR-T cell-induced CRS in situ by conjugating T cell receptor(TCR)-signaling-responsive siltuximab nanogels(NGs)with CAR-T cells.These siltuximab NGs,formed via NHS-S-S-NHS cross-linking,non-covalently bind to CAR-T cells through anti-CD45,significantly prolonging NGs retention time in vivo while preserving the anti-tumor activity of CAR-T cells.Upon excessive activation of CAR-T cells during tumor therapy,the increased reductive environment on the T cell surface triggers the disassembly of siltuximab NGs,releasing siltuximab monomers to inhibit CRS in situ.In a CAR-T cell-mediated CRS mice model,CAR-T@NGs effectively alleviated CRS-related symptoms,such as high fever,weight loss,vascular leakage,coagulation dysfunction,and neurotoxicity.Furthermore,NGs administered in vivo did not cause organ damage and provided a safe and timely treatment for CRS.展开更多
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 i...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.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
基金supported by the Natural Science Foundation of Jilin Province(No.20240101003JJ)the National Natural Science Foundation of China(Nos.22275065,52073116)。
文摘Nanomedicine holds considerable promise for advancing cancer therapy,however,effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake.Herein,we have developed a novel charge-reversible nanogel to deliver paclitaxel(PTX)dimers(DPP)with enhanced stability and targeting precision.The nanogels exhibit a dynamic charge-reversal mechanism responsive to the acidic tumor microenvironment(TME),optimizing the cellular uptake of prodrugs.In the high glutathione(GSH)conditions within cancer cells,the disulfide bonds in the DPP are cleaved,resulting in the intracellular release of active PTX and reduced drug toxicity to normal cells.In vivo pharmacokinetic studies revealed an extended plasma elimination half-life for the charge-reversible nanocarriers,and antitumor efficacy studies demonstrated superior tumor suppression with minimal systemic toxicity.This research underscores the potential of integrating charge-reversal and responsive release mechanisms into one nanocarrier system,balancing the long circulation and high tumor cell internalization capacity of the nanocarrier,and providing a promising strategy for targeted delivery of nanomedicine.
基金supported by the National Key Research and Development Program of China(Grant No.:2022YFC2403200)the National Natural Science Foundation of China(Grant No.:52173289)the National Science Fund for Distinguished Young Scholars,China(Grant No.:52125305).
文摘Reactive oxygen species(ROS)-mediated anticancer modalities,which disturb the redox balance of cancer cells through multi-pathway simulations,hold great promise for effective cancer management.Among these,cooperative physical and biochemical activation strategies have attracted increasing attention because of their spatiotemporal controllability,low toxicity,and high therapeutic efficacy.Herein,we demonstrate a nanogel complex as a multilevel ROS-producing system by integrating chloroperoxidase(CPO)into gold nanorod(AuNR)-based nanogels(ANGs)for cascade-amplifying photothermal-enzymatic synergistic tumor therapy.Benefiting from photothermal-induced hyperthermia upon near-infrared(NIR)laser exposure,the exogenous ROS(including H2O2)were boosted by the AuNR nanogel owing to the intercellular stress response.This ultimately promoted the efficient enzyme-catalyzed reaction of loaded CPO combined with the rich endogenous H2O2 in tumor cells to significantly elevate intracellular ROS levels above the threshold for improved therapeutic outcomes.Both in vitro and in vivo studies have verified the cascade-amplifying ROS-mediated antitumor effects,providing feasible multimodal synergistic tactics for tumor treatment.
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–vip 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-vip 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-vip 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 vip 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-vip 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.
文摘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.
文摘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.
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 China Earthquake Administration under Grant No.20150112National Natural Science Foundation of China under Grant No.21504014
文摘The present paper develops the scaling theory of polyelectrolyte nanogels in dilute and semidilute solutions. The dependencies of the nanogel dimension on branching topology, charge fraction, subchain length, segment number, solution concentration are obtained. For a single polyeleetrolyte nanogel in salt free solution, the nanogel may be swelled by the Coulombie repulsion （the so-called polyelectrolyte regime） or the osmotic eounterion pressure （the so-called osmotic regime）. Characteristics and boundaries between different regimes of a single polyelectrolyte nanogel are summarized. In dilute solution, the nanogels in polyeleetrolyte regime will distribute orderly with the increase of concentration. While the nanogels in osmotic regime will always distribute randomly. Different concentration dependencies of the size of a nanogel in polyeleetrolyte regime and in osmotic regime are also explored.
基金supported by the Science and Technology Commission of Shanghai Municipality(24490711000,23520712500,20DZ2254900)the National Natural Science Foundation of China(U23A2096,2350710203,W2433053,W2421104)the National Key R&D Program of China(2024YFE0108100)。
文摘Developing multifunctional nanoplatforms capable of addressing the excessive oxidative stress and cytokine storm in inflammatory diseases remains a challenging task.Herein,we report the construction of stimuli-responsive nanogels(NGs)through a reverse microemulsion method utilizing taxifolin(Tax)-functionalized generation 3 poly(amidoamine)dendrimers as a monomer and diselenide compound as a crosslinker.Subsequently,exosomes derived from mesenchymal stem cells(MSC-Exos)were coated on the surface of the NGs.The formed multifunctional biomimetic NGs(MSC@DT-NGs)with an average size of 78.3 nm exhibit good colloidal stability and hydrogen peroxide/pH-dual responsive drug release behavior.Meanwhile,the MSCExo coating affords the NGs with excellent macrophage targeting ability to enter the target cells via the clathrin-mediated endocytosis pathway,effectively alleviating intracellular excessive oxidative stress and balancing the antioxidant system through the incorporated anti-oxidant Tax.Furthermore,the MSC@DT-NGs polarize activated macrophages towards the anti-inflammatory M2 phenotype and quell the cytokine storm by inhibiting the intracellular nuclear factor-kappa B signaling pathway.Notably,the MSC@DT-NGs effectively repair lung injury and alleviate acute lung injury(ALI)symptoms by controlling pulmonary inflammation,reducing oxidative stress levels,as well as inhibiting neutrophil infiltration as demonstrated by an ALI mouse model.This study presents an innovative dual-responsive biomimetic nanoplatform that integrates Tax and MSC-Exos for targeted antioxidant delivery and immunomodulation,providing a translational strategy for treating inflammatory disorders.
基金support from the National Science Foundation(CHE-2213445 and 2117699)the University of North Dakota(Early Career Scholars Award).
文摘To date,more biodegradable polymers have been developed due to the growing recognition of the advantages of biodegradable and biocompatible polymers for biomedical applications.In this study,we introduce the synthesis and characterization of innovative polymers that incorporate biodegradable backbones composed of trimethylol-propane and adipic acid moieties and biocleavable side chains containing pyridyl disulfide groups.Notably,their synthesis is straightforward and catalyst-free under ambient conditions,minimizing potential toxicity and immune responses caused by catalyst residues in polymer materials.The new polymers have desired molecular weight(Mn:18.8 kDa)with a narrow dispersion(PDI:1.32)and offer complete biodegradability,biocompatibility,crosslinking capabilities,and opportunities for covalent chemical modifications.These features make them particularly suitable for use in biomedical materials and devices.Additionally,due to their unique properties,these polymers have been successfully formulated into polymeric gels and nanogels,which are biodegradable as well.Using a near-infrared fluorescent probe as a model cargo,we demonstrated the creation of a biosafe and sustainable nanogel system for agent delivery,with an average size of approximately 70 nm.In these nanogels,agent molecules are covalently attached to the scaffold,thereby avoiding uncontrolled premature release and burst release in the bloodstream and mitigating associated systemic toxicity and side effects.The nanogels can also be easily functionalized with targeting ligands for disease-specific delivery.These polymers induced minimal toxicity toward human cells and displayed excellent in vivo biocompatibility,highlighting the significant potential of their polymeric gels and nanogels for a broad spectrum of biomedical applications.
基金supported by the National Key Research and Development Program of China(2023YFB3810001)the National Natural Science Foundation of China(62175198,52333007,U22A2092,and 52273197)+4 种基金the Shenzhen Key Laboratory of Functional Aggregate Materials(ZDSYS20211021111400001)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ2021324134613038,KQTD20210811090142053,JCYJ20220818103007014,and GJHZ20210705141810031)the Innovation and Technology Commission(ITC-CNERC14SC01)the Science and Technology Program of Guangzhou,China(2023A04J0069)the Fundamental Research Funds for the Central Universities(xtr062022002 and xzy022022007).
文摘Photodynamic therapy(PDT)is a promising cancer treatment that uses photosensitizers(PSs)to generate cytotoxic reactive oxygen species(ROS)under light;but improving its efficacy is crucial for clinical applications.To address this;we propose a smart nanoplatform(P@BAO-DOX)for synergistic chemo-photodynamic therapy;featuring efficient PDT;controllable drug release;and fluorescence imaging guidance.We designed an aggregation-induced emission(AIE)-based PS(BAO)with effective ROS generation and NIR-II fluorescence.Additionally;BAO as a PS and doxorubicin(DOX)as a chemo drug were encapsulated in p H-responsive nanogels(PNA)to obtain P@BAO-DOX nanogels.Upon uptake by tumor cells;the nanogel releases drugs in acidic conditions;leading to cell death.White light irradiation further triggers BAO to produce substantial ROS;enhancing phototoxicity and synergistic chemo-PDT cancer therapy.Thus;P@BAO-DOX nanogels;as a smart nanoplatform;offer precise drug release and efficient ROS generation for imaging-guided chemo-PDT synergistic therapy;showing promise in advancing cancer treatment.
基金supported by the National Natural Science Foundation of China(Nos.U23A2089,and 22403070)the National Postdoctoral Program for Innovative Talents(No.BX20230268)+4 种基金the China Postdoctoral Science Foundation(No.2023M742690)the Natural Science Foundation of Hubei Province(No.2025AFA009)Beijing Key Laboratory of High-Entropy Energy materials and Devices(Beijing Institute of Nanoenergy and Nanosystems,Nos.GS2025ZD007 and GS2025MS019)Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202402)the Large-scale Instrument and Equipment Sharing Foundation of Wuhan University.
文摘Chimeric antigen receptor T-cells(CAR-T)therapy has demonstrated significant anti-tumor responses in hematological malignancies and even solid tumors.However,the overactivation of CAR-T cells in vivo can lead to cytokine release syndrome(CRS),with the unpredictable timing and severity of its onset making it difficult to manage effectively.In this study,a strategy was proposed to prevent and treat CAR-T cell-induced CRS in situ by conjugating T cell receptor(TCR)-signaling-responsive siltuximab nanogels(NGs)with CAR-T cells.These siltuximab NGs,formed via NHS-S-S-NHS cross-linking,non-covalently bind to CAR-T cells through anti-CD45,significantly prolonging NGs retention time in vivo while preserving the anti-tumor activity of CAR-T cells.Upon excessive activation of CAR-T cells during tumor therapy,the increased reductive environment on the T cell surface triggers the disassembly of siltuximab NGs,releasing siltuximab monomers to inhibit CRS in situ.In a CAR-T cell-mediated CRS mice model,CAR-T@NGs effectively alleviated CRS-related symptoms,such as high fever,weight loss,vascular leakage,coagulation dysfunction,and neurotoxicity.Furthermore,NGs administered in vivo did not cause organ damage and provided a safe and timely treatment for CRS.
基金National Natural Science Foundation of China(No.21971177,82072051)Natural Science Foundation of the Jiangsu Higher Education Institution of China(No.22KJA150004)+2 种基金Priority Academic Program Development(PAPD)of Jiangsu Higher Education InstitutionsJiangsu Key Laboratory of Advanced Functional Polymers Design and Application,Soochow UniversitySuzhou Key Laboratory of Macromolecular Design and Precision Synthesis and the Program of Innovative Research Team of Soochow University.
文摘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.
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.
