Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising canc...Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.展开更多
基金supported by the Liaoning Provincial Department of Education youth project(No.LJKQZ20222355,China).
文摘Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.