Photoactive Folic acid nanocomposite for targeted PDT of Breast and liver Cancer cell lines

Cancer is a pervasive global health challenge, with breast and liver cancers being at the forefront. A novel treatment approach involves using chitosan nanocarriers and the photosensitizing agent pheophorbide-a to selectively target and eradicate cancer cells through folic acid (FO)-guided laser activation. Building on our prior breakthroughs in photothermal therapy (PTT) using gold nanorods, this study synthesizes and characterizes Pheophorbide-a@Chitosan-folic acid nanocomposites (Pha@CH-FO NC) for targeted photodynamic therapy (PDT). Results demonstrate synergistic ROS-mediated cytotoxicity in breast and liver cancer cells (IC50: 122.74 µg/mL for MCF7), with apoptosis confirmed via Bcl-2 downregulation (60–70%, p < 0.001). This dual-modal approach, integrating PDT with PTT insights, advances precision oncology. The synthesized Pheophorbide-a@Chitosan nanoparticles conjugated with folic acid (Pha@CH-FO NC) underwent thorough characterization by FTIR, TEM, UV-VIS, and HPLC analyses. Results from MTT assays showed that Pha@CH-FO NC had modest cytotoxicity profiles, with IC50 values of 122.74 µg/mL for MCF7 and 217.27 µg/mL for T-47D. There were no discernible IC50 values for MDA-MB-231 and HepG2 cell lines after a 24-hour incubation period. Moreover, when MCF7 and T-47D cells were exposed to half the IC50 of Pha@CH-FO NC combined with laser irradiation (405 nm, 50 mW/96 seconds), they exhibited 50% cytotoxicity. MDA-MB-231 and HepG2 cells showed comparable effects under laser irradiation of 10 mW/500 seconds. Apoptosis was the predominant mode of cell death in all treated cell lines, as evidenced by a decrease in Bcl-2 gene expression (an apoptosis-suppressing gene) in treated cell lines compared to controls. Additionally, increased production of reactive oxygen species (ROS) was observed in irradiated MCF7 and T-47D cells at 50 mW/96 seconds, MDA-MB-231 cells at 50 mW/200 seconds, and HepG2 cells at 10 mW/1000 seconds. This study highlights the potential of Pha@CH-FO NC in enhancing PDT effectiveness and inhibiting cancer progression, making it a crucial component in targeted cancer therapies. The evaluation of various photodynamic approaches underscores the potential of this novel photoactive NC system in advancing PDT and cancer treatment paradigms.