A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a cat...A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a catalyst for the polymerization reaction system.And polytetrahydrofuran with high molecular weight and narrow molecular weight distribution could be obtained.The proposed mechanism was studied by MALDI-TOF,ESI-MS and O-18 isotope labeling analyses as a metal-free coordination insertion mechanism.展开更多
Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of po...Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species(ROS)-responsive drug release.The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization(ROP)of 1,4-dithian-substituted L-glutamate N-carboxyanhydride(DTG-NCA)monomer using an amino-terminated poly(ethylene glycol)methyl ether(mPEG-NH2)as the macro molecular initiator.The resulta nt block copolyme r,mPEG-b-PDTG,could self-assemble into unifo rm micelles in aqueous medium owing to its amphiphilic structure.Then,the H2 O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering(DLS),FT-IR and turbidimetric assay.It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles.Furthermore,the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug.MTT assay also proved that mPEG-b-PDTG was non-toxic in B16 F10 and L929 cells.Therefore,such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.展开更多
Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the p...Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate.Therefore,early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical.In this study,a sulfur dioxide(SO_(2))polymer prodrug was designed as both an intracellular glutathione(GSH)-responsive SO_(2) generator and a carrier of doxorubicin(DOX),and used for the treatment of subcutaneous and metastatic melanoma.Firstly,chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid(DIBA)onto the side chains of methoxy poly(ethylene glycol)grafted dextran(mPEG-g-Dex)resulted in the synthesis of the amphiphilic polymer prodrug of SO_(2),mPEG-g-Dex(DIBA).The obtained mPEG-g-Dex(DIBA)could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO_(2) release behavior.Subsequently,DOX was encapsulated into the core of mPEG-g-Dex(DIBA)micelles to form DOX-loaded nanoparticles(PDDN-DOX).The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO_(2) into the tumor cells.As a result,PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO_(2) and toxic effects of DOX.Furthermore,in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma.Collectively,our present work demonstrates that the combination of SO_(2)-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases.展开更多
基金funded by the National Key R&D Program of China(No.2021YFA1501700)the Science and Technology Development Plan of Jilin Province(Nos.20230101042JC,20210201059GX)+2 种基金the National Natural Science Foundation of China,Basic Science Center Program(No.51988102)the National Natural Science Foundation of China(Nos.52203017,52073272 and 22293062)Bureau of International Cooperation Chinese Academy of Sciences(No.029GJHZ2023017MI)。
文摘A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a catalyst for the polymerization reaction system.And polytetrahydrofuran with high molecular weight and narrow molecular weight distribution could be obtained.The proposed mechanism was studied by MALDI-TOF,ESI-MS and O-18 isotope labeling analyses as a metal-free coordination insertion mechanism.
基金financially supported by the National Natural Science Foundation of China(52222307,51803072,and 51833010)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(20210504001GH)。
基金financially supported by National Key Research and Development Program of China(No.2016YFC1100701)the National Natural Science Foundation of China(Nos.51573184,51520105004 and 51833010)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2017266)。
文摘Stimuli-re sponsive polypeptides have been intensively investigated fo r controlled drug release,owing to their favorable biocompatibility and biodegradability.In this work,we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species(ROS)-responsive drug release.The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization(ROP)of 1,4-dithian-substituted L-glutamate N-carboxyanhydride(DTG-NCA)monomer using an amino-terminated poly(ethylene glycol)methyl ether(mPEG-NH2)as the macro molecular initiator.The resulta nt block copolyme r,mPEG-b-PDTG,could self-assemble into unifo rm micelles in aqueous medium owing to its amphiphilic structure.Then,the H2 O2-triggered oxidation behaviors of the mPEG-b-PDTG micelles were studied by dynamic light scattering(DLS),FT-IR and turbidimetric assay.It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles.Furthermore,the ROS-responsive drug release behavior of the mPEG-b-PDTG micelles was verified by using Nile Red as a model drug.MTT assay also proved that mPEG-b-PDTG was non-toxic in B16 F10 and L929 cells.Therefore,such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.
基金supported by the National Natural Science Foundation of China(51803209,51773196,and 51573184)the Jilin Provincial Science and Technology Development Program(20190201205JC,20190103022JH,and 20190103038JH)the Youth Innovation Promotion Association of Chinese Academy and Sciences(2017266).
文摘Melanoma,as the most aggressive and treatment-resistant skin malignancy,is responsible for about 80%of all skin cancer mortalities.Prone to invade into the dermis and form distant metastases significantly reduce the patient survival rate.Therefore,early treatment of the melanoma in situ or timely blocking the deterioration of metastases is critical.In this study,a sulfur dioxide(SO_(2))polymer prodrug was designed as both an intracellular glutathione(GSH)-responsive SO_(2) generator and a carrier of doxorubicin(DOX),and used for the treatment of subcutaneous and metastatic melanoma.Firstly,chemical conjugation of 4-N-(2,4-dinitrobenzenesulfonyl)-imino-1-butyric acid(DIBA)onto the side chains of methoxy poly(ethylene glycol)grafted dextran(mPEG-g-Dex)resulted in the synthesis of the amphiphilic polymer prodrug of SO_(2),mPEG-g-Dex(DIBA).The obtained mPEG-g-Dex(DIBA)could self-assemble into stable micellar nanoparticles and exhibited a glutathione-responsive SO_(2) release behavior.Subsequently,DOX was encapsulated into the core of mPEG-g-Dex(DIBA)micelles to form DOX-loaded nanoparticles(PDDN-DOX).The formed PDDN-DOX could be internalized by B16F10 cells and synchronously release DOX and SO_(2) into the tumor cells.As a result,PDDN-DOX exerted synergistic anti-tumor effects in B16F10 melanoma cells because of the oxidative damage properties of SO_(2) and toxic effects of DOX.Furthermore,in vivo experiments verified that PDDN-DOX had great potential for the treatment of subcutaneous and metastasis melanoma.Collectively,our present work demonstrates that the combination of SO_(2)-based gas therapy and chemotherapeutics offers a new avenue for inhibiting melanoma progression and metastases.
