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, PB 3 C 60 and PB 3 C 70 , together with their precursor porphyrin PB 3 OH, 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, PB 3 C 60 and PB 3 C 70 , and precursor PB 3 OH 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. PB 3 C 60 exhibited the highest selective phototoxicity in gliomblastoma cells under PDT, inducing apoptosis with moderate ROS and mitochondrial fragmentation. PB 3 OH caused nonspecific cytotoxicity via excessive ROS, while PB 3 C 70 triggered apoptosis even without light. PB 3 C 60 showed strong potential as a targeted photosensitizer for glioblastoma, with light‐dependent selectivity for cancer cells. Unlike PB 3 OH and PB 3 C 70 , its apoptotic effect was both specific and light activated, highlighting PB 3 C 60 's promise as a nanohybrid therapeutic for glioblastoma.