Minimizing Adverse Effects of Cerenkov Radiation Induced Photodynamic Therapy With Transformable Photosensitizer-loaded Nanovesicles
Abstract BackgroundPhotodynamic 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 (CR-PDT) induced by Cerenkov radiation (CR) has deeper tissue penetration than traditional PDT. While the combination strategy by coupling radionuclides with photosensitizers might cause severe side effects. MethodsWe designed tumor-targeting nanoparticles ( 131 I-EM@ALA) by loading 5-Aminolevulinic acid (ALA) into 131 I-labeled exosome mimetic (EM) to achieve combined antitumor therapy. In addition to the role of radiotherapy, 131 I can also serve as an internal light source for its Cerenkov radiation (CR). ResultsThe drug-loaded nanoparticles could effectively target tumors as confirmed by confocal imaging, flow cytometry, and small animal fluorescence imaging. The in vitro and in vivo experiments demonstrated that 131 I-EM@ALA produced a promising antitumor effect by synergizing radiotherapy and CR-PDT. The nanoparticles killed tumor cells by inducing DNA damage and activating the lysosome-mitochondrial pathways. During the treatment, there were no obvious abnormalities found in hematology analyses, blood biochemistry, and histological examinations. ConclusionsWe successfully engineered nanocarrier coloaded with radionuclide 131 I and a photosensitizer precursor for combinational radiotherapy and PDT in treatment of breast cancer.