Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics

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 significant...

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Veröffentlicht in:	Journal of nanobiotechnology Jg. 19; H. 1; S. 112 - 15
Hauptverfasser:	Zhou, Liqiang, Huo, Minfeng, Qian, Xiaoqin, Ding, Li, Yu, Luodan, Feng, Wei, Cui, Xinwu, Chen, Yu
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 20.04.2021 BioMed Central Ltd Springer Nature B.V BMC
Schlagworte:	Animal models Animals Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Apoptosis - radiation effects Autophagy Autophagy (Cytology) Autophagy - drug effects Autophagy inhibition Biotechnology Cancer Cancer therapies Care and treatment Cell culture Cell Line, Tumor Cell survival Chemistry Chemistry and Materials Science Combinatorial analysis Female Health aspects Humans Kinases MAP kinase MCF-7 Cells Mice Mice, Inbred BALB C Mice, Nude Molecular Medicine Nanoliposomes Nanoparticles Nanoparticles - chemistry Nanoparticles - therapeutic use Nanotechnology Neoplasms - therapy Oxidation resistance Oxidative stress Phagocytosis Polyethylene glycol Proteins Protoporphyrin Protoporphyrin IX Protoporphyrins - pharmacology Radiation Radiation-Sensitizing Agents Signal transduction Signaling Sonication - methods Sonodynamic therapy Survival Synergistic effect Transcriptome Tumor therapy Tumors Ultrasonic imaging Ultrasonic Therapy - methods Ultrasonics in medicine Ultrasound China United States > US Nanoliposomes Autophagy Tumor therapy Sonodynamic therapy Autophagy inhibition
ISSN:	1477-3155, 1477-3155
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1477-3155 1477-3155
DOI:	10.1186/s12951-021-00855-y