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. Effective photodynamic therapy induces cancer damage and death through a multifactorial manner including reactive oxygen species-mediated damage and killing, vasculature damage, and immune defense activation. Anticancer efficiency depends on the improvement of photosensitizers drugs used in photodynamic therapy, 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 need for developing improved photosensitizers for photodynamic applications and achieving better therapeutic outcomes. Bioconjugation and encapsulation with targeting moieties appear as a main strategies for the development of photosensitizers from their precursors. Factors influencing 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 still mainly in the developmental stage.