Mitochondria-based photodynamic anti-cancer therapy.

As photodynamic therapy (PDT) becomes established as a treatment for cancer, there is increasing interest in identifying critical mechanisms of cell killing and understanding the bases for effective photosensitizers. The existence of multiple cellular targets makes it difficult to distinguish the critical events leading to cell death from PDT. However, with more sensitive techniques to detect photosensitizer localization, the isolation of PDT-resistant and -sensitive mutants and the use of innovative molecular and biochemical strategies to map cellular events occurring during and after photosensitization, some order is emerging from the chaos. The subcellular localization of many photosensitizers and the early responses to light activation indicate that mitochondria play a major role in photodynamic cell death. PDT with many agents which damage or inhibit different or multiple mitochondrial targets has many of the desirable characteristics for an effective anti-cancer therapy.