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Minimizing adverse effects of Cerenkov radiation induced photodynamic therapy with transformable photosensitizer-loaded nanovesicles

BACKGROUND: Photodynamic therapy (PDT) is a promising antitumor strategy with fewer adverse effects and higher selectivity than conventional therapies. Recently, a series of reports have suggested that PDT induced by Cerenkov radiation (CR) (CR-PDT) has deeper tissue penetration than traditional PDT...

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Detalles Bibliográficos
Autores principales: Qian, Ruijie, Wang, Kun, Guo, Yawen, Li, Hongyan, Zhu, Ziyang, Huang, Xiaojuan, Gong, Chengpeng, Gao, Yu, Guo, Rong, Yang, Biao, Wang, Chenyang, Jiang, Dawei, Lan, Xiaoli, An, Rui, Gao, Zairong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044600/
https://www.ncbi.nlm.nih.gov/pubmed/35477389
http://dx.doi.org/10.1186/s12951-022-01401-0
Descripción
Sumario:BACKGROUND: Photodynamic therapy (PDT) is a promising antitumor strategy with fewer adverse effects and higher selectivity than conventional therapies. Recently, a series of reports have suggested that PDT induced by Cerenkov radiation (CR) (CR-PDT) has deeper tissue penetration than traditional PDT; however, the strategy of coupling radionuclides with photosensitizers may cause severe side effects. METHODS: We designed tumor-targeting nanoparticles ((131)I-EM@ALA) by loading 5-aminolevulinic acid (ALA) into an (131)I-labeled exosome mimetic (EM) to achieve combined antitumor therapy. In addition to playing a radiotherapeutic role, (131)I served as an internal light source for the Cerenkov radiation (CR). RESULTS: The drug-loaded nanoparticles effectively targeted tumors as confirmed by confocal imaging, flow cytometry, and small animal fluorescence imaging. In vitro and in vivo experiments demonstrated that (131)I-EM@ALA produced a promising antitumor effect through the synergy of radiotherapy and CR-PDT. The nanoparticles killed tumor cells by inducing DNA damage and activating the lysosome-mitochondrial pathways. No obvious abnormalities in the hematology analyses, blood biochemistry, or histological examinations were observed during the treatment. CONCLUSIONS: We successfully engineered a nanocarrier coloaded with the radionuclide (131)I and a photosensitizer precursor for combined radiotherapy and PDT for the treatment of breast cancer. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01401-0.