Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor treatment.However,two main issues hamper the antitumor performance of PDT:overexpressio...Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor treatment.However,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor microenvironment.The drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective treatment.To address these issues,a MnO_(2)doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and MnO_(2)loading.The surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell penetration.After internalization,HTIM-PMs showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO_(2)and ICG.The released MnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT effect.The PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS diffusion.These PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of PTT.This promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.展开更多
基金financial support from the National Natural Science Foundation of China(Nos.82172090 and 82072059)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-058 and 2022-I2M-1-023)+1 种基金Fundamental Research Funds for the Central Universities(No.2019PT320028)Tianjin Municipal Natural Science Foundation(No.20JCYBJC00030)。
文摘Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor treatment.However,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor microenvironment.The drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective treatment.To address these issues,a MnO_(2)doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and MnO_(2)loading.The surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell penetration.After internalization,HTIM-PMs showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO_(2)and ICG.The released MnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT effect.The PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS diffusion.These PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of PTT.This promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.
