Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is a...Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is always desired at the tissue interface.In this study,inspired by the principle that like charges repulse each other,a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers,thus realizing unidirectional gene therapy at the tendon-paratenon interface.Under the charge repulsion of positively charged layer,more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue,which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation,but also avoided adverse effects on the fragile endogenous healing of tendon itself.In summary,this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.展开更多
The design of advanced binders plays a critical role in stabilizing the cycling performance of large-volume-effect silicon monoxide(SiO)anodes.For the classic polyacrylic acid(PAA)binder,the self-association of-COOH g...The design of advanced binders plays a critical role in stabilizing the cycling performance of large-volume-effect silicon monoxide(SiO)anodes.For the classic polyacrylic acid(PAA)binder,the self-association of-COOH groups in PAA leads to the formation of intramolecular and intermolecular hydrogen bonds,greatly weakening the bonding force of the binder to SiO surface.However,strengthening the binder-material interaction from the perspective of binder molecular regulation poses a significant challenge.Herein,a modified PAA-Li_(x)(0.25≤x≤1)binder with prominent mechanical properties and adhesion strength is specifically synthesized for SiO anodes by quantitatively substituting the carboxylic hydrogen with lithium.The appropriate lithium substitution(x=0.25)not only effectively increases the number of hydrogen bonds between the PAA binder and SiO surface owing to charge repulsion effect between ions,but also guarantees moderate entanglement between PAA-Li_x molecular chains through the ion-dipole interaction.As such,the PAA-Li_(0.25)/SiO electrode exhibits exceptional mechanical properties and the lowest volume change,as well as the optimum cycling(1237.3 mA h g^(-1)after 100cycles at 0.1 C)and rate performance(1000.6 mA h g^(-1)at 1 C),significantly outperforming the electrode using pristine PAA binder.This work paves the way for quantitative regulation of binders at the molecular level.展开更多
基金supported by the National Natural Science Foundation of China (No.82172408 and 81902234)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829)+1 种基金Program of Shanghai Academic/Technology Research Leader (22XD1422600)Shanghai Municipal Health Commission (Grant No.2022YQ073).
文摘Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is always desired at the tissue interface.In this study,inspired by the principle that like charges repulse each other,a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers,thus realizing unidirectional gene therapy at the tendon-paratenon interface.Under the charge repulsion of positively charged layer,more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue,which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation,but also avoided adverse effects on the fragile endogenous healing of tendon itself.In summary,this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.
基金supported by the National Natural Science Foundation of China (Grant Nos.92372101,52162036 and 21875155)the Fundamental Research Funds for the Central Universities (Grant Nos.20720220010)the National Key Research and Development Program of China (Grant Nos.2021YFA1201502)。
文摘The design of advanced binders plays a critical role in stabilizing the cycling performance of large-volume-effect silicon monoxide(SiO)anodes.For the classic polyacrylic acid(PAA)binder,the self-association of-COOH groups in PAA leads to the formation of intramolecular and intermolecular hydrogen bonds,greatly weakening the bonding force of the binder to SiO surface.However,strengthening the binder-material interaction from the perspective of binder molecular regulation poses a significant challenge.Herein,a modified PAA-Li_(x)(0.25≤x≤1)binder with prominent mechanical properties and adhesion strength is specifically synthesized for SiO anodes by quantitatively substituting the carboxylic hydrogen with lithium.The appropriate lithium substitution(x=0.25)not only effectively increases the number of hydrogen bonds between the PAA binder and SiO surface owing to charge repulsion effect between ions,but also guarantees moderate entanglement between PAA-Li_x molecular chains through the ion-dipole interaction.As such,the PAA-Li_(0.25)/SiO electrode exhibits exceptional mechanical properties and the lowest volume change,as well as the optimum cycling(1237.3 mA h g^(-1)after 100cycles at 0.1 C)and rate performance(1000.6 mA h g^(-1)at 1 C),significantly outperforming the electrode using pristine PAA binder.This work paves the way for quantitative regulation of binders at the molecular level.