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

Abstract

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

Global Trends and Research Progress of Photodynamic Therapy in Skin Cancer: A Bibliometric Analysis and Literature Review

“…32 Besides, PDT can induce tumor cell necrosis through the activation of receptor-interacting protein kinase 1 (RIPK1), lysosome damage, and intracellular calcium overload. 33,34 Cell death could also be triggered by PDT via immunogenic way by the emission of damage-associated molecular patterns (DAMP), including HSP70, HSP90, HMGB1 and IL-1β. 35,36 Figure 6 Journal analysis in the field of PDT on skin cancer.…”

Multifunctional nanoparticle for cancer therapy

“…Qian et al. 343 designed multifunctional nanoparticles ( 131 I‐EM@ALA) based on 131 I‐labeled exosome mimetic (EM) to deliver 5‐aminolevulinic acid (ALA). 4T 1 cancer cell membranes squeezed together and modified by the amine groups in ALA to obtain EM@ALA. 131 I was radiolabeled EM@ALA by the chloramine T method, forming 131 I‐EM@ALA.…”

“…Due to the protein in exosomes, there are many amine groups, thiol groups, and carboxyl groups that can be covalently modified by other functional groups, such as amino groups. Qian et al 343 . designed multifunctional nanoparticles ( 131 I‐EM@ALA) based on 131 I‐labeled exosome mimetic (EM) to deliver 5‐aminolevulinic acid (ALA).…”

“…Due to the protein in exosomes, there are many amine groups, thiol groups, and carboxyl groups that can be covalently modified by other functional groups, such as amino groups. Qian et al 343 designed multifunctional nanoparticles ( 131 I-EM@ALA) based on 131 I-labeled exosome mimetic (EM) to deliver 5aminolevulinic acid (ALA). 4T 1 cancer cell membranes squeezed together and modified by the amine groups in ALA to obtain EM@ALA. 131 I was radiolabeled EM@ALA by the chloramine T method, forming 131 I-EM@ALA.…”

Combining Radiotherapy (RT) and Photodynamic Therapy (PDT): Clinical Studies on Conventional RT-PDT Approaches and Novel Nanoparticle-Based RT-PDT Approaches under Preclinical Evaluation

“…Chen et al tested several common photosensitizers for use with FDG in Cherenkov radiation-induced PDT and identified vertoporfin as the best choice . While radionuclides have an innate ability to emit UV, their own cell kill effects are not comparable with that of external beam RT. Thus, Cherenkov-induced PDT is unable to produce the synergistic effects of PDT and RT.…”