A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl co...A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through ＂turn-on＂ chromogenic and fluorogenic dual modes.展开更多
Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjug...Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.展开更多
The widespread use of polymeric materials has brought unparalleled convenience and utility,but their environmental persistence presents a critical and growing challenge.As demand increases for sustainable solutions to...The widespread use of polymeric materials has brought unparalleled convenience and utility,but their environmental persistence presents a critical and growing challenge.As demand increases for sustainable solutions to polymer waste,depolymerization continues to be a promising strategy for achieving true circularity.In this Perspective,we examine depolymerization from a fundamental standpoint,aiming to rationalize the advantages,limitations,and future directions of state-ofthe-art technologies.We advocate for standardized reporting practices to enable meaningful comparisons across studies and,in alignment with this goal,we provide key metrics and contextual information throughout the article to support consistent evaluation of different depolymerization strategies.Ultimately,we hope to inspire readers to explore innovative and scalable solutions that advance the transformative potential of depolymerization toward the realization of a circular polymer economy.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone.RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the ...Rheumatoid arthritis(RA)is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone.RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints.Herein,we developed a biomimetic formulation via co-loading the anti-inflammatory agent Celastrol(Cel)along with the stabilizer Vitamin K(VK)in antirheumatic methotrexate(MTX)-conjugated Pluronic F127(F127)micelles.Micelles were then coated with B cell derived membrane,yielding MTX loaded Cel Micelle(CeViM)-micelle@B,which were investigated for RA treatment.VK,used at levels well within safety margins,was identified as a carrier compound that could stabilize Cel within micelles,increasing the encapsulation efficiency of Cel.In addition,MTX,a front-line RA therapeutic,was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments.As such,CeViM-micelle@B released pristine MTX in response to the intracellular reducing environments,which combined with Cel to suppress pro-inflammatory responses.B cell membrane coating enhanced accumulation of CeViM-micelle@B in joints,leading to a 75%decrease of inflammatory cytokine secretion in vitro,and significantly ameliorated cartilage and bone structures in the collagen-induced arthritis murine model.Taken together,this biomimetic nanoparticle holds potential as a nextgeneration targeted RA treatment.展开更多
基金financial support from National Natural Science Foundation of China (No. 21202099)the Science Foundation of Shanghai Institute of Technology (No. YJ2011-75)the Opening Fund of Shanghai Key Laboratory of Chemical Biology (No. SKLCB-2014-01)
文摘A new chromogenic and fluorescent ＂turn-on＂ chemodosimeter 3 was designed and synthesized by using a fluoride-sensitive self-immolative linker, in combination with the fluorescent dyes 7-hydroxy-4-trifluoromethyl coumarin. The chemodosimeter exhibited high selectivity and sensitivity toward fluoride anions through ＂turn-on＂ chromogenic and fluorogenic dual modes.
基金supported by Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University。
文摘Self-immolative linkers have been widely used to construct prodrugs to improve their efficacy and safety.In this study,we report the use of phenoxysilyl linker as a self-immolative unit to prepare antibody-drug conjugates(ADCs).Phenoxysily based ADC Ate-PPS-CA4 was prepared and its release was systematically investigated by mass spectrometry.Biological evaluation showed that Ate-PPS-CA4 displayed the ability to target delivery and self-immolative release the active payload CA4 on PD-L1 positive cells MDA-MB-231.As the same with its payload CA4,it could arrest the cell cycle to the G2/M phase and induced changes in cell morphology at the dose of its IC_(50).The development of this linker with novel drug release mechanisms will expand the methodology to construct ADCs,especially for non-internalizing ADCs by extracellular cleavage.
基金financial support through the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany’s Excellence Strategy−EXC-2193/1−390951807financial support through faculty startup funds provided by the Department of Chemistry at the University of Utahfinancial support through faculty startup funds provided by the Department of Chemistry at Northeastern University.
文摘The widespread use of polymeric materials has brought unparalleled convenience and utility,but their environmental persistence presents a critical and growing challenge.As demand increases for sustainable solutions to polymer waste,depolymerization continues to be a promising strategy for achieving true circularity.In this Perspective,we examine depolymerization from a fundamental standpoint,aiming to rationalize the advantages,limitations,and future directions of state-ofthe-art technologies.We advocate for standardized reporting practices to enable meaningful comparisons across studies and,in alignment with this goal,we provide key metrics and contextual information throughout the article to support consistent evaluation of different depolymerization strategies.Ultimately,we hope to inspire readers to explore innovative and scalable solutions that advance the transformative potential of depolymerization toward the realization of a circular polymer economy.
基金This work was supported by the National Natural Science Foundation of China(22375144 and 32071384)the National Key Research and Development Program(2021YFC2102300)+1 种基金the basic research project of Shanxi Science and Technology Department(202103021224342)Key Research and Development(R&D)Projects of Shanxi Province(2021XM01).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that leads to the destruction of articular cartilage and bone.RA is characterized by immune cell infiltration and abnormal proliferation of synoviocytes in the joints.Herein,we developed a biomimetic formulation via co-loading the anti-inflammatory agent Celastrol(Cel)along with the stabilizer Vitamin K(VK)in antirheumatic methotrexate(MTX)-conjugated Pluronic F127(F127)micelles.Micelles were then coated with B cell derived membrane,yielding MTX loaded Cel Micelle(CeViM)-micelle@B,which were investigated for RA treatment.VK,used at levels well within safety margins,was identified as a carrier compound that could stabilize Cel within micelles,increasing the encapsulation efficiency of Cel.In addition,MTX,a front-line RA therapeutic,was chemically grafted to F127 via a responsive linker sensitive to the chemically reducing environments.As such,CeViM-micelle@B released pristine MTX in response to the intracellular reducing environments,which combined with Cel to suppress pro-inflammatory responses.B cell membrane coating enhanced accumulation of CeViM-micelle@B in joints,leading to a 75%decrease of inflammatory cytokine secretion in vitro,and significantly ameliorated cartilage and bone structures in the collagen-induced arthritis murine model.Taken together,this biomimetic nanoparticle holds potential as a nextgeneration targeted RA treatment.
