Biophysical and Biological Features of Third Generation Photosensitizers Used in Anticancer Photodynamic Therapy: Review.

Cancer remains a main public health issue and the second cause of mortality worldwide. Photodynamic therapy is a clinically approved therapeutic option for several conditions and can induce damages in localized tumors. Effective photodynamic therapy induces cancer damage and death through a multifactorial manner including reactive oxygen species-mediated direct cancer damage and killing, tumor vasculature damage, and immune defense activation. Its anticancer efficiency depends on the improvement of photosensitizers, drugs used in photodynamic therapy, considering their selectivity, enhanced photoproduction of reactive species, absorption at near-infrared spectrum, and drug-delivery strategies. Both experimental and clinical studies using first- and second-generation photosensitizers had pointed out the urgent need for developing improved photosensitizers for photodynamic applications and achieving better therapeutic outcomes. Bioconjugation and encapsulation with targeting moieties appeared as the main strategies for the new development of photosensitizers from their precursors. Factors influencing their cellular biodistribution and uptake are briefly discussed, as well as their roles as cancer diagnostic and therapeutic (theranostics) agents. The two-photon photodynamic approach using third-generation photosensitizers is present as an attempt in treating deeper tumors. Although significant advances had been made over the last decade, the development of next-generation photosensitizers is promising and should be conducted via chemo- and site-selective manner to facilitate PDT translation into further stages of treatment and cancer management.