We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepa...We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.展开更多
Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to che...Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.展开更多
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
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 polymerizat...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.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
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 ima...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.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
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 ...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.展开更多
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 photosens...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.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
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...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.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
Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulat...Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.展开更多
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...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.展开更多
A series of random copolypeptides of poly（methoxy-diethylene glycol–L-glutamate）-co-poly（S-（onitrobenzyl）-L-cysteine）was synthesized by ring-open copolymerization of methoxydiethylene glycol-Lglutamate-N-carbox...A series of random copolypeptides of poly（methoxy-diethylene glycol–L-glutamate）-co-poly（S-（onitrobenzyl）-L-cysteine）was synthesized by ring-open copolymerization of methoxydiethylene glycol-Lglutamate-N-carboxyanhydride（EG2-Glu-NCA） and S-（o-nitrobenzyl）-L-cysteine-N-carboxyanhydride（NBC-NCA） in dried dimethylformamide solution, which presents quadruple thermo-photo-redox responsive self-assembly behavior and forms the related nanogel and hydrogel in water.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
The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phe...The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.展开更多
Here we report a novel polymeric nanogel with stable loading cargo and near-infrared(NIR) controlled release properties.The nanogels are crosslinked by quaternization reactions of biocompatible poly(β-amino esters) a...Here we report a novel polymeric nanogel with stable loading cargo and near-infrared(NIR) controlled release properties.The nanogels are crosslinked by quaternization reactions of biocompatible poly(β-amino esters) and diselenide-bonded crosslinker(DSe DCl) in microemulsions.The hydrophobic cavities of the nanogels have the property of stably encapsulating the hydrophobic vip molecules,resulted from the crosslinked network structure.Due to the redox responsiveness of the diselenide bonds on the DSe DCl crosslinker,the nanogels can respond to oxidant H_(2)O_(2) causing the disintegration of the crosslinked network structure,thus the encapsulated vip cargo molecules will be released.It is noted that,upon loading the photosensitizer IR780,the nanogels can generate reactive oxygen species(ROS) under NIR irradiation to release the cargo.The advantages of encapsulated cargo stability enhanced by chemical cross-linking and remote stimulation response performance via NIR offer great potential of nanogels for applications of cargo controlled release.展开更多
基金Funded by the Tianjin Municipal Education Commission(No.2022ZD041)。
文摘We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.
基金financially supported by the National Natural Science Foundation of China(No.82102908)the Natural Science Foundation of Tianjin of China(No.22JCQNJC01260)+3 种基金Natural Science Foundation of Hebei Province of China(No.H2024202004)National Natural Science Foundation of China(No.U23A6008)National Key Research and Development Program of China(No.2023YFC2412300)Natural Science Foundation of Hebei Province of China(No.H2022202007)。
文摘Despite the considerable potentiality of photodynamic therapy(PDT)in cancer treatment,conventional hydrophobic photosensitizers cause obstacles for in vivo application,while their inert structures are difficult to chemically modify.Additionally,undesirable tumor hypoxia resulting from oxygen consumption also discounts the therapeutic efficacy of PDT.Herein,we developed a self-strengthened nanogel with reactive oxygen species(ROS)trigger-explosive property.IR780 was spontaneous assembled within the conical cavity of cyclodextrin(β-CD)using host-vip interactions,while adjacent IR780 molecules on the dextrin backbone with hydrophobic interaction andπconjugation induced nanogel formation.Simultaneously,hydrophilic compound tirapazamine(TPZ)was incorporated into nanogel for synergistic tumor treatment.The inherent high levels of ROS in tumor can break down boronic ester bond linker of nanogel,initiating its disintegration.Furthermore,our findings indicate the ROS level(including H2O2and1O2)can be transiently enhanced during PDT process at the animal level,which accelerates the explosion of nanogel.Notably,the IR780@β-CD module exhibited enhanced ROS generation efficiency during PDT with the continues explosion of nanogel,which further strengthens nanogel disintegration,tumor phototherapy and cargo releasement.Additionally,the released TPZ is activated under hypoxic conditions after PDT treatment,addressing the limitations of PDT and facilitating multi-synergistic tumor treatment.
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.
文摘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.
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supported by the Ministry of Oceans and Fisheries,Korea(the project title:Development of marine material based near infrared fluorophore complex and diagnostic imaging instruments)by a Grant(1910070)from the National Cancer Center
文摘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.
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Funded by the National Natural Science Foundation of Hubei Province(No.2014CFB306)the National Natural Science Foundation of China(No.51772233)+1 种基金the National Key Research and Development Program of China(No.2016YFC1101605)the Science and Technology Support Program of Hubei Province(No.2015BAA085)
文摘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.
基金supported by National Natural Science Foundation of China(Nos.21704074,21621004)Tianjin Natural Science Foundation(Basic Research Plan,Nos.18JCJQJC47600,19JCQNJC02200).
文摘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.
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National Basic Research Program of China(973 Program)(No.2015CB932100)National Natural Science Foundation of China(No.81473165)+1 种基金Liaoning Provincial Key Laboratory of Drug Preparation Design&Evaluation of Liaoning Provincial Education Department(LZ2014045)Liaoning Provincial Key Laboratory of Studying the Modern Drug preparations.
文摘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.
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.
基金supported by the National Natural Science Foundation of China(Grant No.U23A20591,52203201,52173149,and 81971174)the Youth Talents Promotion Project of Jilin Province(Grant No.202019)+1 种基金the Science and Technology Development Program of Jilin Province(Grant No.20210101114JC)Research Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin University(Grant No.KYXZ2022JC04).
文摘Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
基金This research was supported by Fundacao para a Ciencia e a Tecnologia under grant SFRH/BD/22242/2005.
文摘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.
基金the financial support of the National Natural Science Foundation of China (No. 21474061)
文摘A series of random copolypeptides of poly（methoxy-diethylene glycol–L-glutamate）-co-poly（S-（onitrobenzyl）-L-cysteine）was synthesized by ring-open copolymerization of methoxydiethylene glycol-Lglutamate-N-carboxyanhydride（EG2-Glu-NCA） and S-（o-nitrobenzyl）-L-cysteine-N-carboxyanhydride（NBC-NCA） in dried dimethylformamide solution, which presents quadruple thermo-photo-redox responsive self-assembly behavior and forms the related nanogel and hydrogel in water.
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the National Natural Science Foundation of China(Nos.51922043,52173122 and 31771091)Guangdong Provincial Program(No.2017GC010304)+1 种基金Science and Technology Planning Project of Ganzhou(No.202101074816)Fundamental Research Funds for Central Universities.
文摘The existence of tumor immunosuppressive microenvironment(TIME)is the major determinant for the poor efficacy of current tumor immunotherapy.Tumor-associated macrophages(TAMs)tend to become tumor-promoting M2-like phenotype and hinder immune response in solid tumors.Repolarization of TAMs from M2 to anti-tumor M1 phenotype is robust for remodeling the TIME.Herein,we developed a redox-responsive nanogel as the delivery system of Toll-like receptor 7 and 8(TLR7/8)agonist(R848)prodrug for potent cancer immunotherapy.The nanogel(denoted as R848-Gel)was obtained by emulsion polymerization of HSEMA and R848 prodrug(R848-HSEMA),whose size was appropriate 100 nm.R848-Gel could be internalized by macrophages and dendritic cells in vitro,and effectively repolarized M2 into M1 macrophages and promoted the maturation of antigen-presenting cells.In vivo study indicated that the R848-Gel showed a stronger tumor inhibitory effect and no drastic body weight change compared with free drug.Immune cell analysis after the treatment indicated that R848-Gel was helpful to activating the TIME.In summary,this study provides a simple but effective vehicle for R848 to improve cancer immunotherapy.
基金financially supported by the National Natural Science Foundation of China (No. 51373025)the Program for New Century Excellent Talents in University (No. NCET-110582)。
文摘Here we report a novel polymeric nanogel with stable loading cargo and near-infrared(NIR) controlled release properties.The nanogels are crosslinked by quaternization reactions of biocompatible poly(β-amino esters) and diselenide-bonded crosslinker(DSe DCl) in microemulsions.The hydrophobic cavities of the nanogels have the property of stably encapsulating the hydrophobic vip molecules,resulted from the crosslinked network structure.Due to the redox responsiveness of the diselenide bonds on the DSe DCl crosslinker,the nanogels can respond to oxidant H_(2)O_(2) causing the disintegration of the crosslinked network structure,thus the encapsulated vip cargo molecules will be released.It is noted that,upon loading the photosensitizer IR780,the nanogels can generate reactive oxygen species(ROS) under NIR irradiation to release the cargo.The advantages of encapsulated cargo stability enhanced by chemical cross-linking and remote stimulation response performance via NIR offer great potential of nanogels for applications of cargo controlled release.
