Background Traditional photodynamic therapy (PDT) is limited by low penetration of light in the tissue. Cherenkov radiation-induced PDT (CR-PDT) uses Cherenkov luminescence from charged particles passing through the tissue as an internal light source to excite photosensitizers (PS) used to treat deep tumors. Methods This systematic review was carried out according to PRISMA 2020 protocols and was registered in the PROSPERO database (CRD420261309392). PubMed, Web of Science, and Scopus databases were searched (January 2015-February 2026). Sixteen preclinical studies (14 in vitro/in vivo, 2 early translational) were included after screening 894 records. Results Beta-emitters (primarily 89 Zr, 18 F-FDG, 90 Y) activated diverse PS, frequently nanoparticle-encapsulated (e.g., mesoporous silica nanoparticles, extracellular vesicles, or graphene oxide hybrids), producing reactive oxygen species (ROS) via Type I/II mechanisms. In vitro, dose-dependent reductions in metabolic activity (assessed by MTT/MTS assays and flow cytometry), which reflect acute biological response but not clonogenic survival in two studies) reached >70-80% reduction in cell viability with optimized nanoplatforms. In vivo, significant tumor growth regression and survival benefits were observed in animal models (murine breast, ovarian, liver, and pancreatic xenografts). Cherenkov luminescence imaging (CLI) provided inherent theranostic monitoring of distribution and response. The risk of bias (ROB) was low in general. Conclusion CR-PDT represents an experimental preclinical strategy for internally activated theranostic PDT in deep-seated tumor models. Nanotechnology enhances efficacy, but clinical translation requires standardized dosimetry and larger studies.
Mohammed et al. (Mon,) studied this question.