Photodynamic Anticancer Efficacy of meso-tris-p-Carboxyphenylporphyrin-Fullerene Dyads: Apoptosis Induction and Mitochondrial Deregulation in Glioblastoma Therapy.

This work explores the toxicity profile and anticancer mechanisms of reported anti-HIV carboxyphenyl porphyrin-fullerene dyads, PB3C60 and PB3C70, together with their precursor porphyrin PB3OH, within noncationic porphyrin-based donor-π-acceptor (D-π-A) assemblies. This study evaluates the patented compounds meso-tris-p-carboxyphenyl porphyrin-fullerene (P-F) dyads, PB3C60 and PB3C70, and precursor PB3OH within noncationic donor-π-acceptor (D-π-A) assemblies as amphiphilic photosensitizers (PSs) for glioblastoma photodynamic therapy (PDT). Emphasis is placed on light-induced apoptosis, mitochondrial disruption in glioma-derived cells, along with the already reported anti-HIV properties, indicating potential for dual-action therapy in immunocompromised individuals. Given the critical need for therapies effective in immunocompromised patients, further investigation into noncationic P-F dyads could yield dual-action agents. P-F dyads were administered to tumour-derived as well as nontransformed cells and subjected to PDT. PB3C60 exhibited the highest selective phototoxicity in gliomblastoma cells under PDT, inducing apoptosis with moderate ROS and mitochondrial fragmentation. PB3OH caused nonspecific cytotoxicity via excessive ROS, while PB3C70 triggered apoptosis even without light. PB3C60 showed strong potential as a targeted photosensitizer for glioblastoma, with light-dependent selectivity for cancer cells. Unlike PB3OH and PB3C70, its apoptotic effect was both specific and light activated, highlighting PB3C60's promise as a nanohybrid therapeutic for glioblastoma.