Abstract
Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention ow-ing to their great potential for tumor treatment.However,two main issues hamper the antitumor per-formance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reac-tive oxygen species(ROS),and hypoxia within the tumor microenvironment.The drawbacks of PTT in-clude 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 MnO2 doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indo-cyanine green(ICG)and MnO2 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 glu-tathione,high H2O2).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO2 and ICG.The released MnO2 further reduced the GSH level and promoted O2 gener-ation,thus enhancing the PDT effect.The PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O2 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.
基金项目
National Natural Science Foundation of China(82172090)
National Natural Science Foundation of China(82072059)
CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-058)
CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M-1-023)
Fundamental Research Funds for the Central Universities(2019PT320028)
Tianjin Municipal Natural Science Foundation(20JCYBJC00030)
万方数据