Minimizing Adverse Effects of Cerenkov Radiation Induced Photodynamic Therapy With Transformable Photosensitizer-loaded Nanovesicles

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.

Photodynamic Therapy Excited by Cerenkov Radiation from Cesium-137 Irradiator: In Vitro Studies

Photodynamic therapy (PDT) is a non-invasive cancer therapy method that has been clinically approved for many years. Due to strong optical scattering and absorption of tissues, optical photons can only penetrate tissues several millimetres, which limits the applications of PDT to superficial lesions. To overcome the limitation of penetration depth, here we applied Cerenkov radiation, as generated by the high-energy -rays from radionuclide Cesium-137, to directly activate the porphyrin-based photosensitizer MPPa (Pyropheophorbide-a methyl ester) without any additional energy mediators. Experiments were conducted with A549 human lung carcinoma cell line. Moreover, to reduce the effects of possible plastic scintillation on PDT, we used black cell culture plates in these studies. We have also shown that the effects of the scintillations on PDT could be minimized. In our studies, we have excluded the effects of radiotherapy and drug toxicity. Our results indicated that the Cerenkov radiation generated from high energy -rays could be used to activate the photosensitizer MPPa in PDT, which could potentially overcome the penetration limitations of optical photon-based PDT, making the PDT a feasible and complementary cancer therapy for deep lesions.