O2-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

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外文摘要：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.

外文关键词：

Photodynamic therapyPhotothermal therapyOxygen generatingOne-step self-assemblyStimuli-responsive nanoparticles

作者：

Yu Qin、Mingyang Huang、Chenlu Huang、Hannah L.Perry、Linhua Zhang、Dunwan Zhu

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作者单位：

Tianjin Key Laboratory of Biomedical Materials,Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300192,China

Molecular Sciences Research Hub,Department of Chemistry,White City Campus,Imperial College London,London W12 0BZ,United Kingdom

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCAMS Innovation Fund for Medical Sciences(CIFMS)CAMS Innovation Fund for Medical Sciences(CIFMS)Fundamental Research Funds for the Central UniversitiesTianjin Municipal Natural Science Foundation

项目编号：

82172090820720592021-I2M-1-0582022-I2M-1-0232019PT32002820JCYBJC00030

出版年：

2024

DOI：

10.1016/j.cclet.2023.109171

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCD

影响因子：0.771

ISSN：1001-8417

年,卷(期)：2024.35(7)