Synergic mechanisms of photothermal and photodynamic therapies mediated by photosensitizer/carbon nanotube complexes

We report the construct of a nanosystem based on multi-walled carbon nanotubes (MWCNT) and the photosensitizer m-tetrahydroxyphenylchlorin (mTHPC) for cancer treatment by combination of photodynamic (PDT) and photothermal (PTT) therapy. The photoactivity of the complex mTHPC/MWCNT was studied revealing quenching of the photosensitizer associated to CNT and almost total release of the photosensitizer into the cell cytoplasm after uptake by SKOV3 ovarian cancer cells. The photothermal and photodynamic cytotoxicity of these mTHPC/MWCNT on/off complexes was assessed at the cell level by viability test, imaging flow cytometry, confocal microscopy and transmission electron microscopy and at the molecular level by a proteomic analysis of apoptosis-related proteins and genomic analysis of 84 genes involved in oxidative stress. Cytotoxicity correlated at the cell level to the uptake of mTHPC/MWCNT, while PDT and PTT treatment induced different signaling pathways leading to cell apoptosis. For the first time, the mechanisms of PDT/PTT synergy in eradication of cancer cells were studied revealing that distinct cell responses to PDT and PTT defeat the cell defense to oxidative stress.