Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics
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 si...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-04-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00855-y |
| _version_ | 1798026574685011968 |
|---|---|
| author | Liqiang Zhou Minfeng Huo Xiaoqin Qian Li Ding Luodan Yu Wei Feng Xinwu Cui Yu Chen |
| author_facet | Liqiang Zhou Minfeng Huo Xiaoqin Qian Li Ding Luodan Yu Wei Feng Xinwu Cui Yu Chen |
| author_sort | Liqiang Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T18:37:29Z |
| format | Article |
| id | doaj.art-58cc01a2c90e4b9e8dfe0087902e7126 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:37:29Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-58cc01a2c90e4b9e8dfe0087902e71262022-12-22T04:09:10ZengBMCJournal of Nanobiotechnology1477-31552021-04-0119111510.1186/s12951-021-00855-yAutophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeuticsLiqiang Zhou0Minfeng Huo1Xiaoqin Qian2Li Ding3Luodan Yu4Wei Feng5Xinwu Cui6Yu Chen7Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyState Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of SciencesDepartment of Ultrasound, Affiliated People’s Hospital of Jiangsu UniversityState Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of SciencesSchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologySchool of Life Sciences, Shanghai UniversityAbstract 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.https://doi.org/10.1186/s12951-021-00855-yAutophagySonodynamic therapyAutophagy inhibitionNanoliposomesTumor therapy |
| spellingShingle | Liqiang Zhou Minfeng Huo Xiaoqin Qian Li Ding Luodan Yu Wei Feng Xinwu Cui Yu Chen Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics Journal of Nanobiotechnology Autophagy Sonodynamic therapy Autophagy inhibition Nanoliposomes Tumor therapy |
| title | Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics |
| title_full | Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics |
| title_fullStr | Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics |
| title_full_unstemmed | Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics |
| title_short | Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics |
| title_sort | autophagy blockade synergistically enhances nanosonosensitizer enabled sonodynamic cancer nanotherapeutics |
| topic | Autophagy Sonodynamic therapy Autophagy inhibition Nanoliposomes Tumor therapy |
| url | https://doi.org/10.1186/s12951-021-00855-y |
| work_keys_str_mv | AT liqiangzhou autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT minfenghuo autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT xiaoqinqian autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT liding autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT luodanyu autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT weifeng autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT xinwucui autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics AT yuchen autophagyblockadesynergisticallyenhancesnanosonosensitizerenabledsonodynamiccancernanotherapeutics |