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

• Main Authors: An, R. (Author), Gao, Y. (Author), Gao, Z. (Author), Gong, C. (Author), Guo, R. (Author), Guo, Y. (Author), Huang, X. (Author), Jiang, D. (Author), Lan, X. (Author), Li, H. (Author), Qian, R. (Author), Wang, C. (Author), Wang, K. (Author), Yang, B. (Author), Zhu, Z. (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2022
• Subjects: 5-Aminolaevulinic acid; 5-aminolevulinic acid; Adverse effect; Breast cancer; Breast Cancer; Cerenkov radiation; Diseases; Exosome coating; Exosomes; Fluorescence imaging; Light sources; Medical nanotechnology; Mimetics; Nanomedicine; Nanoparticles; Nuclear medicine; Photodynamic therapy; Photosensitiser; Photosensitizers; Radiation effects; Radioisotopes; Radiotherapy; Synergistic therapy; Targeted drug delivery; Tumors
• Online Access: View Fulltext in Publisher
• ISBN: 14773155 (ISSN)
• DOI: 10.1186/s12951-022-01401-0

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 (131I-EM@ALA) by loading 5-aminolevulinic acid (ALA) into an 131I-labeled exosome mimetic (EM) to achieve combined antitumor therapy. In addition to playing a radiotherapeutic role, 131I 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 131I-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 131I and a photosensitizer precursor for combined radiotherapy and PDT for the treatment of breast cancer. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s).