Photosensitizer Targeting: Mitochondrion-Targeted Photosensitizer Enhances Mitochondrial Reactive Oxygen Species and Mitochondrial Calcium-Mediated Apoptosis

Abstract

Using laser scanning imaging microscopy, our previous studies have demonstrated visible laser irradiation induced significant generation of mitochondrial reactive oxygen species (mROS) and apoptosis. In addition, photodynamic therapy (PDT) with a mitochondrion-targeted photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), significantly enhanced visible laser irradiation induced mitochondrial dysfunction and apoptosis. To validate the critical role of the mitochondrion as well as how mitochondrial mechanisms were involved in the PDT of BPD-MA, subcellular PDT with BPD-MA were performed using region irradiation and recorded by multi-photon imaging microscopy coupled with mitochondrial specific fluorescent probes in single live C6 glioma cells. Specifically, mROS and mitochondrial free calcium (mCa²⁺) were simultaneously measured from cells received subcellular PDT with BPD-MA in different compartments including the mitochondrion, the cytosol and the nucleus. Results revealed that significant formation of mROS accompanied by elevation of mCa²⁺ was found only in the mitochondrial PDT with BPD-MA. Subsequently, mitochondrial PDT with BPD-MA resulted in severe mitochondrial swelling, plasma membrane blebing and apoptotic death. We conclude that via augmented mROS formation and mCa²⁺ elevation PDT with a mitochondrion-targeted photosensitizer extensively enhances mitochondria-mediated apoptosis and, thus, may provide high eradication efficacy for clinical cancer treatment.