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

利用可转化光敏剂纳米囊泡最大限度地减少切伦科夫辐射诱导的光动力疗法的副作用

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作者:Ruijie Qian #, Kun Wang #, Yawen Guo, Hongyan Li, Ziyang Zhu, Xiaojuan Huang, Chengpeng Gong, Yu Gao, Rong Guo, Biao Yang, Chenyang Wang, Dawei Jiang, Xiaoli Lan, Rui An, Zairong Gao

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.

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.

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.

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