2. Academic Validation
  3. Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics

Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics

  • J Nanobiotechnology. 2021 Apr 20;19(1):112. doi: 10.1186/s12951-021-00855-y.
Liqiang Zhou 1,  Minfeng Huo 2,  Xiaoqin Qian 3,  Li Ding 4,  Luodan Yu 5,  Wei Feng 5,  Xinwu Cui 6,  Yu Chen 7 8
Affiliations

Affiliations

  • 1 Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
  • 2 State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China.
  • 3 Department of Ultrasound, Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, People's Republic of China.
  • 4 State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China. dlgood2006@mail.sic.ac.cn.
  • 5 School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.
  • 6 Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. cuixinwu@hust.edu.cn.
  • 7 School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China. chenyuedu@shu.edu.cn.
  • 8 State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, People's Republic of China. chenyuedu@shu.edu.cn.
PMID: 33879173 DOI: 10.1186/s12951-021-00855-y
Abstract

Ultrasound-triggered sonodynamic therapy (SDT) represents an emerging therapeutic modality for Cancer treatment based on its specific feature of noninvasiveness, high tissue-penetrating depth and desirable therapeutic efficacy, but the SDT-induced pro-survival cancer-cell Autophagy would significantly lower the SDT efficacy for Cancer treatment. Here we propose an "all-in-one" combined tumor-therapeutic strategy by integrating nanosonosensitizers-augmented noninvasive SDT with Autophagy inhibition based on the rationally constructed nanoliposomes that co-encapsulates clinically approved sonosensitizers protoporphyrin IX (PpIX) and early-phase autophagy-blocking agent 3-methyladenine (3-MA). It has been systematically demonstrated that nanosonosensitizers-augmented SDT induced cytoprotective pro-survival Autophagy through activation of MAPK signaling pathway and inhibition of AMPK signaling pathway, and this could be efficaciously inhibited by 3-MA in early-phase Autophagy, which significantly decreased the cell resistance to intracellular oxidative stress and complied a remarkable synergistic effect on SDT medicated cancer-cell Apoptosis both in vitro at cellular level and in vivo on tumor-bearing animal model. Therefore, our results provide a proof-of-concept combinatorial tumor therapeutics based on nanosonosensitizers for the treatment of ROS-resistant Cancer by Autophagy inhibition-augmented SDT.

Keywords

Autophagy; Autophagy inhibition; Nanoliposomes; Sonodynamic therapy; Tumor therapy.

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