Albumin-Phthalocyanine Nanoconjugates as Platforms for Enhanced Photodynamic Cancer Therapy.

This study investigates the enhancement of photodynamic therapy (PDT) efficacy through the encapsulation of platinum phthalocyanine (Pc) in albumin nanoparticles (ANP). Encapsulation of Pc in ANP) significantly enhances its biological effects in photodynamic therapy by increasing cellular uptake through receptor-mediated endocytosis and promoting lysosomal accumulation. This leads to marked lysosomal stress and regulated necrotic cell death pathway, while free Pc causes moderate oxidative stress with reversible apoptosis and autophagy. The enhanced phototoxicity of encapsulated Pc was evident across multiple cancer cell lines, especially aggressive phenotypes, whereas resistant lines showed lower sensitivity likely due to efficient ROS scavenging. Despite improved initial uptake, rapid lysosomal release and extracellular extrusion of Pc limit long-term intracellular retention. Morphological and gene expression analyses confirmed distinct cell death mechanisms between free and encapsulated Pc, underscoring the critical role of nanocarrier-mediated delivery in modulating oxidative stress and cellular response. These findings highlight the importance of nanoparticle design in optimizing PDT efficacy by effectively triggering necrotic cell death pathway.