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
Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,endowing PEG-PLA m...Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,endowing PEG-PLA micelles with high drug loading,self-assembly stability and fast intracellular drug release is still challenging.Redox-responsive diblock copolymers(MPEG-SS-PMLA)of poly(ethylene glycol)and phenyl-functionalized poly(lactic acid)with disulfide bond as the linker are synthesized to prepare PLA-based micelles that demonstrate excellent colloidal stability and high Ru loading.Notably,MPEGSS-PMLA achieved a remarkably high Ru loading efficiency of 84.3%due to the existence of strongπ-πstacking between phenyl and Ru complex.MPEG-SS-PMLA exhibited good colloidal stability in physiological condition but quickly destabilized by reductive tumor microenvironment.Interestingly,about 74%of Ru complex was released under 10 mmol/L GSH concentration.Ru-loaded MEPG-SS-PMLA showed efficient delivery and release of Ru complex into MCF-7 cancer cells,achieving enhanced in vitro and in vivo antitumor activity of photodynamic therapy.This feasible functionalization method of MPEG-PLA has appeared to be a clinically viable platform for controlled delivery therapeutic agents and enhanced phototherapy.展开更多
A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAG...A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAGP)) and AgNPs is developed to deliver the anti-cancer drug camptothecin(CPT) and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence( "off" state) due to the nanoparticle surface energy transfer(NSET) effect.Upon the exposure to glutathione(GSH), the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT("on" state). The system offers a platform to track the CPT delivery and releasing in real time展开更多
Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of h...Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of high molecular mass and overall hydrophilicity of proteins creating extremely poor permeability across cell membrane.Hence,there remains an unmet need to develop safe,potent approaches to augment intracellular protein delivery efficiency.Here,we described a facile multicomponent reaction system for generating a small library of redox-responsive cationic polypeptoids with high biocompatibility.The co-assembly of optimized polymer with protein leads to the formation of compacted nanocomplexes with smaller size and high encapsulation efficiency,thus improving cellular internalization via the macropinocytosis and/or caveolae-mediated endocytosis mainly.After endo-lysosomal escape,the nanocomplexes can be disassociated to efficiently release cargo proteins into the cytosol,owing to the intracellular glutathione(GSH)-triggered rapid cleavage of disulfide bonds in polymers backbone.As a result,we screened a promising platform reagent for efficient cytosolic protein delivery application.展开更多
The molecular assembling properties can be dramatically improved using redox-responsive nanoplatforms, which can bring quite different aggregation modes and binding behaviors in the redox states. In this work, we fabr...The molecular assembling properties can be dramatically improved using redox-responsive nanoplatforms, which can bring quite different aggregation modes and binding behaviors in the redox states. In this work, we fabricated a redox-responsive system based on the host–guest complexation of b-cyclodextrin(b-CD) with ferrocene-modified diphenylalanine(Fc-FF). The morphological conversion of Fc-FF can be easily achieved from nanofibers to nanospheres in the presence of b-CD, and the supramolecular nanospheres can be reversibly assembled and disassembled by the chemical redox of ferrocenyl groups in the Fc-FF&b-CD nanoassemblies. These results demonstrate that the incorporation of stimuli-switchable components with macrocyclic receptors may become a promising approach to the construction of smart peptide-involved supramolecular assemblies.展开更多
Many anticancer drugs have limited clinical applications owing to their unsatisfactory therapeutic efficacy or side effects.This situation can be improved by drug delivery systems or drug modification strategies.Herei...Many anticancer drugs have limited clinical applications owing to their unsatisfactory therapeutic efficacy or side effects.This situation can be improved by drug delivery systems or drug modification strategies.Herein,to improve the therapeutic efficacy and safety of the traditional anticancer drug 6-mercaptopurine(6-MP),we dimerized 6-MP to form a disulfide bond-containing drug dimer and prepared a cysteine-based poly(disulfide amide)with redox-responsive capability as a drug carrier.Briefly,dimeric 6-MP(DMP)was synthesized via the oxidization of iodine and self-assembled with the poly(disulfide amide)to form dual redox-responsive DMP-loaded NPs(DMP-NPs).The 6-MP itself could hardly be loaded into nanoparticles(NPs)owing to its hydrophobicity,while the DMP-NPs showed a higher drug loading capacity over 6-MP,small particle size,and favorable stability.With abundant disulfide bonds in polymer backbones and drug payloads,DMP-NPs could rapidly respond to high levels of glutathione(GSH)and release drugs in a controllable manner.More importantly,both cellular and animal experiments demonstrated the enhanced anticancer efficacy of DMP-NPs against lymphoma and their high safety.Overall,this drug dimer-loaded dual redox-responsive drug delivery system provides new options for improving the applications of traditional drugs and developing drug delivery systems with enhanced drug effects and high safety.展开更多
Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,a...Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.展开更多
The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical...The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian(Camelus bactrianus) CSA. The constructed CSA nanoparticles(CSA-NPs)with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite(CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione(GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drugdelivery matrix to exert synergistic effects.展开更多
An inclusion-interaction assembly strategy was used to construct novel pH/redox responsive core-shell micelles with hydrophobic drug as the core and hydrophilic polymer as the shell. At first, a dimer of hydrophobic d...An inclusion-interaction assembly strategy was used to construct novel pH/redox responsive core-shell micelles with hydrophobic drug as the core and hydrophilic polymer as the shell. At first, a dimer of hydrophobic drug 6-mercaptopurine and a hydrophilic β-CD grafted carboxymethyl chitosan were synthesized. Then, a novel amphiphilic inclusion complex was prepared with the dimer being partially embedded into the cavity of β-CD moiety. It self-assembled into pH/redox responsive core-shell micelles in distilled water. TEM confirmed that the micelles possessed a spherical core-shell configuration with a mean size of about 160 nm. DLS showed that the micelles were stable in aqueous solution. Their particle diameters altered with pH values as well as glutathione (GSH) concentrations and respectively attained a maximum value at pH 6.0 and 20 mM GSH. Release profiles of 6-mercaptopurine showed a low release rate (about 27 wt% after 48 h) in pH 7.4 medium with 10 μM GSH, and a marked increase (over 88 wt% after 48 h) in pH 5.0 medium with 20 mM GSH. In vitro cytotoxicity test showed that the micelles had a dose-dependent toxicity for HeLa cells, indicating a great potential for controlled release of 6-mercaptopurine in tumor cells.展开更多
Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic trib...Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL.To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles.The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination therapy.Hence,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.展开更多
Antioxidant biomaterials have attracted much attention in various biomedical fields because of their effective inhibition and elimination of reactive oxygen species(ROS)in pathological tissues.However,the difficulty i...Antioxidant biomaterials have attracted much attention in various biomedical fields because of their effective inhibition and elimination of reactive oxygen species(ROS)in pathological tissues.However,the difficulty in ensuring biocompatibility,biodegradability and bioavailability of antioxidant materials has limited their further development.Novel bioavailable antioxidant materials that are derived from natural resources are urgently needed.Here,an integrated multi-omics method was applied to fabricate antioxidant biomaterials.A key cysteine-rich thrombospondin-1 type Ⅰ repeat-like(TSRL)protein was efficiently discovered from among 1262 adhesive components and then used to create a recombinant protein with a yield of 500 mg L^(-1).The biocompatible TSRL protein was able to self-assemble into either a water-resistant coating through Ca^(2+)-mediated coordination or redox-responsive hydrogels with tunable physical properties.The TSRL-based hydrogels showed stronger 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging rates than glutathione(GSH)and ascorbic acid(Aa)and protected cells against external oxidative stress significantly more effectively.When topically applied to mice skin,TSRL alleviated epidermal hyperplasia and suppressed the degradation of collagen and elastic fibers caused by ultraviolet radiation B(UVB)irradiation,confirming that it enhanced antioxidant activity in vivo.This is the first study to successfully characterize natural antioxidant biomaterials created from marine invertebrate adhesives,and the findings indicate the excellent prospects of these biomaterials for great applications in tissue regeneration and cosmeceuticals.展开更多
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financially supported by the National Science Foundation of China(Nos.22022803,22078046,21808028)Science and Technology Foundation of Liaoning Province(Nos.2019BS-047,2021-YGJC-17)Fundamental Research Funds for the Central Universities(No.DUT20YG131)。
文摘Poly(ethylene glycol)-poly(lactic acid)block copolymer(PEG-PLA)is one of the most widely used biomedical polymers in clinical drug delivery owing to its biocompatibility and biodegradability.However,endowing PEG-PLA micelles with high drug loading,self-assembly stability and fast intracellular drug release is still challenging.Redox-responsive diblock copolymers(MPEG-SS-PMLA)of poly(ethylene glycol)and phenyl-functionalized poly(lactic acid)with disulfide bond as the linker are synthesized to prepare PLA-based micelles that demonstrate excellent colloidal stability and high Ru loading.Notably,MPEGSS-PMLA achieved a remarkably high Ru loading efficiency of 84.3%due to the existence of strongπ-πstacking between phenyl and Ru complex.MPEG-SS-PMLA exhibited good colloidal stability in physiological condition but quickly destabilized by reductive tumor microenvironment.Interestingly,about 74%of Ru complex was released under 10 mmol/L GSH concentration.Ru-loaded MEPG-SS-PMLA showed efficient delivery and release of Ru complex into MCF-7 cancer cells,achieving enhanced in vitro and in vivo antitumor activity of photodynamic therapy.This feasible functionalization method of MPEG-PLA has appeared to be a clinically viable platform for controlled delivery therapeutic agents and enhanced phototherapy.
基金supported by the National Natural Science Foundation of China(No. 21574037)the"100 Talents" Program of Hebei Province, China(No. E2014100004)+2 种基金the Natural Science Foundation of Hebei Province(Nos. B2015202330, B2017202051)the Program for Top 100 Innovative Talents in Colleges and Universities of Hebei Province(No.SLRC2017028)the Tianjin Natural Science Foundation(No. 15JCYBJC17500)
文摘A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[(2-((2-((camptothecin)-oxy)ethyl)disulfanyl)ethylmethacrylate)-co-(2-(D-galactose)methylmethacryl-ate)](P(MACPTS-co-MAGP)) and AgNPs is developed to deliver the anti-cancer drug camptothecin(CPT) and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence( "off" state) due to the nanoparticle surface energy transfer(NSET) effect.Upon the exposure to glutathione(GSH), the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT("on" state). The system offers a platform to track the CPT delivery and releasing in real time
基金This work was supported by the National Natural Science Foundation of China(51803243,51820105004)the Guangdong Basic and Applied Basic Research Foundation(2020A1515011285)the Guangdong Innovative and Entrepreneurial Research Team Program(2013S086).
文摘Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of high molecular mass and overall hydrophilicity of proteins creating extremely poor permeability across cell membrane.Hence,there remains an unmet need to develop safe,potent approaches to augment intracellular protein delivery efficiency.Here,we described a facile multicomponent reaction system for generating a small library of redox-responsive cationic polypeptoids with high biocompatibility.The co-assembly of optimized polymer with protein leads to the formation of compacted nanocomplexes with smaller size and high encapsulation efficiency,thus improving cellular internalization via the macropinocytosis and/or caveolae-mediated endocytosis mainly.After endo-lysosomal escape,the nanocomplexes can be disassociated to efficiently release cargo proteins into the cytosol,owing to the intracellular glutathione(GSH)-triggered rapid cleavage of disulfide bonds in polymers backbone.As a result,we screened a promising platform reagent for efficient cytosolic protein delivery application.
基金National Natural Science Foundation of China (Nos. 21432004, 21472100, 21772099 and 91527301) for financial support
文摘The molecular assembling properties can be dramatically improved using redox-responsive nanoplatforms, which can bring quite different aggregation modes and binding behaviors in the redox states. In this work, we fabricated a redox-responsive system based on the host–guest complexation of b-cyclodextrin(b-CD) with ferrocene-modified diphenylalanine(Fc-FF). The morphological conversion of Fc-FF can be easily achieved from nanofibers to nanospheres in the presence of b-CD, and the supramolecular nanospheres can be reversibly assembled and disassembled by the chemical redox of ferrocenyl groups in the Fc-FF&b-CD nanoassemblies. These results demonstrate that the incorporation of stimuli-switchable components with macrocyclic receptors may become a promising approach to the construction of smart peptide-involved supramolecular assemblies.
基金This work was supported by the National Natural Science Foundation of China(Nos.51973243 and 52173150)International Cooperation and Exchange of the National Natural Science Foundation of China(No.51820105004)+1 种基金China Postdoctoral Science Foundation(No.2020M683058),the Science and Technology Planning Project of Shenzhen(No.JCYJ20190807155801657)Guangdong Innovative and Entrepreneurial Research Team Program(No.2016ZT06S029).
文摘Many anticancer drugs have limited clinical applications owing to their unsatisfactory therapeutic efficacy or side effects.This situation can be improved by drug delivery systems or drug modification strategies.Herein,to improve the therapeutic efficacy and safety of the traditional anticancer drug 6-mercaptopurine(6-MP),we dimerized 6-MP to form a disulfide bond-containing drug dimer and prepared a cysteine-based poly(disulfide amide)with redox-responsive capability as a drug carrier.Briefly,dimeric 6-MP(DMP)was synthesized via the oxidization of iodine and self-assembled with the poly(disulfide amide)to form dual redox-responsive DMP-loaded NPs(DMP-NPs).The 6-MP itself could hardly be loaded into nanoparticles(NPs)owing to its hydrophobicity,while the DMP-NPs showed a higher drug loading capacity over 6-MP,small particle size,and favorable stability.With abundant disulfide bonds in polymer backbones and drug payloads,DMP-NPs could rapidly respond to high levels of glutathione(GSH)and release drugs in a controllable manner.More importantly,both cellular and animal experiments demonstrated the enhanced anticancer efficacy of DMP-NPs against lymphoma and their high safety.Overall,this drug dimer-loaded dual redox-responsive drug delivery system provides new options for improving the applications of traditional drugs and developing drug delivery systems with enhanced drug effects and high safety.
基金supported by the National Natural Science Foundation of China (51922111)the Science and Technology Development Fund, Macao SAR (File no. 0124/2019/A3)+1 种基金the University of Macao (File no. MYRG2022-00203-ICMS)Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials (2019B121205002)
文摘Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
基金supported by National Natural Science Foundation of China(No.U1703118)Natural Science Foundation of Jiangsu Province(No.BK20181364)+6 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJA310003)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Jiangsu Shuangchuang ProgramOpen Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics(No.2016015)Open Project of the National Laboratory of Biomacromolecules(No.2017KF05)the Cooperative Project between Southeast University and Nanjing Medical University(No.2018DN0004)Jiangsu Specially-Appointed Professor Project,China。
文摘The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian(Camelus bactrianus) CSA. The constructed CSA nanoparticles(CSA-NPs)with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite(CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione(GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drugdelivery matrix to exert synergistic effects.
文摘An inclusion-interaction assembly strategy was used to construct novel pH/redox responsive core-shell micelles with hydrophobic drug as the core and hydrophilic polymer as the shell. At first, a dimer of hydrophobic drug 6-mercaptopurine and a hydrophilic β-CD grafted carboxymethyl chitosan were synthesized. Then, a novel amphiphilic inclusion complex was prepared with the dimer being partially embedded into the cavity of β-CD moiety. It self-assembled into pH/redox responsive core-shell micelles in distilled water. TEM confirmed that the micelles possessed a spherical core-shell configuration with a mean size of about 160 nm. DLS showed that the micelles were stable in aqueous solution. Their particle diameters altered with pH values as well as glutathione (GSH) concentrations and respectively attained a maximum value at pH 6.0 and 20 mM GSH. Release profiles of 6-mercaptopurine showed a low release rate (about 27 wt% after 48 h) in pH 7.4 medium with 10 μM GSH, and a marked increase (over 88 wt% after 48 h) in pH 5.0 medium with 20 mM GSH. In vitro cytotoxicity test showed that the micelles had a dose-dependent toxicity for HeLa cells, indicating a great potential for controlled release of 6-mercaptopurine in tumor cells.
基金the National Natural Science Foundation of China(Nos.81671806,81571793)CAMS Initiative for Innovative Medicine(Nos.2017-I2M-4-001,2017-I2M-3-020)Fundamental Re search Funds for the Central Universities(Nos.2019PT320028,2019-0831-03)。
文摘Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer treatment.Herein,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL.To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles.The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination therapy.Hence,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.
基金supported by the Natural Science Foundation of China(32071371,41776177)the Fundamental Research Funds for the Central Universities(201822024,202061011)the China Postdoctoral Science Foundation(2020M672143).
文摘Antioxidant biomaterials have attracted much attention in various biomedical fields because of their effective inhibition and elimination of reactive oxygen species(ROS)in pathological tissues.However,the difficulty in ensuring biocompatibility,biodegradability and bioavailability of antioxidant materials has limited their further development.Novel bioavailable antioxidant materials that are derived from natural resources are urgently needed.Here,an integrated multi-omics method was applied to fabricate antioxidant biomaterials.A key cysteine-rich thrombospondin-1 type Ⅰ repeat-like(TSRL)protein was efficiently discovered from among 1262 adhesive components and then used to create a recombinant protein with a yield of 500 mg L^(-1).The biocompatible TSRL protein was able to self-assemble into either a water-resistant coating through Ca^(2+)-mediated coordination or redox-responsive hydrogels with tunable physical properties.The TSRL-based hydrogels showed stronger 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging rates than glutathione(GSH)and ascorbic acid(Aa)and protected cells against external oxidative stress significantly more effectively.When topically applied to mice skin,TSRL alleviated epidermal hyperplasia and suppressed the degradation of collagen and elastic fibers caused by ultraviolet radiation B(UVB)irradiation,confirming that it enhanced antioxidant activity in vivo.This is the first study to successfully characterize natural antioxidant biomaterials created from marine invertebrate adhesives,and the findings indicate the excellent prospects of these biomaterials for great applications in tissue regeneration and cosmeceuticals.