Photodynamic Anticancer Efficacy of <i>meso</i> ‐tris‐ <i>p</i> ‐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.