Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/...Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/p H-responsive hydrogel system based on poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate)(PEDOT:PSS)for the controlled delivery of pharmacologically active bevacizumab(BEV).The hydrogel system was fabricated via a one-step physical crosslinking process by mixing PEDOT:PSS with BEV,leveraging electrostatic interactions,hydrogen bonding,and ionic crosslinking.The resulting PEDOT@BEV system exhibited a homogeneously porous structure,robust mechanical stability,and good biocompatibility.Under acidic(p H=5)or alkaline(p H=10)conditions,especially when coupled with elevated reactive oxygen species(ROS)levels,the as-prepared PEDOT@BEV achieved rapid BEV release.This may be attributed to PEDOT oxidation and charge repulsion.In contrast,BEV release remained stable under physiological conditions(p H=7.4,0 mmol/L H_(2)O_(2)).In vitro results supported that the resulting PEDOT@BEV demonstrated potent anti-angiogenic efficacy,significantly inhibiting cellular migration and tube formation of human retinal vascular endothelial cells(HRVECs).The vascular endothelial growth factor expression was further reduced.In a mouse model of corneal neovascularization,the PEDOT@BEV system enabled the continuous controlled release of BEV for over 14 days.It exhibited superior anti-angiogenic efficacy compared to free BEV treatment,more effectively reducing neovascularization and corneal inflammation.The designed platform in this work demonstrated versatility by successfully incorporating other therapeutic antibodies(e.g.,rituximab,trastuzumab),highlighting its potential for tailored drug delivery in oncology and neovascular diseases.The outcome of this study offers a promising strategy for spatiotemporally controlled drug release in response to specific microenvironmental cues.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82502583 and U20A20338)Huadong Medicine Joint Funds of Natural Science Foundation of Zhejiang Province(No.LHDMY23H070004)the Summit Advancement Disciplines of Zhejiang Province(Wenzhou Medical University-Pharmaceutics)。
文摘Multiresponsive hydrogels,capable of responding to more than one external stimulus,have demonstrated great utility in biomedical applications.This study presents a facile method for preparing an injectable,dual redox/p H-responsive hydrogel system based on poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate)(PEDOT:PSS)for the controlled delivery of pharmacologically active bevacizumab(BEV).The hydrogel system was fabricated via a one-step physical crosslinking process by mixing PEDOT:PSS with BEV,leveraging electrostatic interactions,hydrogen bonding,and ionic crosslinking.The resulting PEDOT@BEV system exhibited a homogeneously porous structure,robust mechanical stability,and good biocompatibility.Under acidic(p H=5)or alkaline(p H=10)conditions,especially when coupled with elevated reactive oxygen species(ROS)levels,the as-prepared PEDOT@BEV achieved rapid BEV release.This may be attributed to PEDOT oxidation and charge repulsion.In contrast,BEV release remained stable under physiological conditions(p H=7.4,0 mmol/L H_(2)O_(2)).In vitro results supported that the resulting PEDOT@BEV demonstrated potent anti-angiogenic efficacy,significantly inhibiting cellular migration and tube formation of human retinal vascular endothelial cells(HRVECs).The vascular endothelial growth factor expression was further reduced.In a mouse model of corneal neovascularization,the PEDOT@BEV system enabled the continuous controlled release of BEV for over 14 days.It exhibited superior anti-angiogenic efficacy compared to free BEV treatment,more effectively reducing neovascularization and corneal inflammation.The designed platform in this work demonstrated versatility by successfully incorporating other therapeutic antibodies(e.g.,rituximab,trastuzumab),highlighting its potential for tailored drug delivery in oncology and neovascular diseases.The outcome of this study offers a promising strategy for spatiotemporally controlled drug release in response to specific microenvironmental cues.
