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.

Multifunctional nanoparticle for cancer therapy

“…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.…”

Cerenkov radiation-activated probes for deep cancer theranostics: a review

“…Combination therapy also has been developed in which the precursor of protoporphyrin IX called 5-aminolevulinic acid (ALA) and 131 I are co-loaded into biomimetic exosomes. In the tumor microenvironment, where mitochondria are abundant, the ALA is converted to protoporphyrin IX, minimizing CRIT side effects on normal tissues [97].…”