Enhanced in vitro photodynamic therapy for triple-negative breast cancer by pheophorbide a-encapsulated chitosan-tripolyphosphate nanoparticles

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer. Current treatment strategies typically involve surgical resection and chemotherapy, both of which are often associated with significant adverse effects. As an alternative, photodynamic therapy (PDT) offers a minimally invasive approach to selectively target tumor cells. In this work, PDT was evaluated using pheophorbide a (Pa) as a photosensitizer. To enhance its therapeutic efficacy, Pa was encapsulated in ionically crosslinked chitosan/tripolyphosphate (TPP) nanoparticles. Furthermore, nanoparticles synthesized from chitosan subjected to various pre-treatments were compared in terms of their physicochemical properties. The optimized Pa-loaded chitosan/TPP nanoparticles (PaCNPs) exhibited enhanced singlet oxygen (¹O₂) generation upon photoactivation of Pa. Cellular uptake and intracellular distribution of Pa were extensively examined in MDA-MB-453 and MDA-MB-231 cell lines. Notably, nanoparticle encapsulation resulted in a fourfold reduction in IC₅₀ in MDA-MB-231 cells, whereas no significant change was observed in MDA-MB-453 cells. The distinct responses of these cell lines to PaCNPs-mediated PDT in are further discussed.