Phototoxicity of zinc oxide nanoparticle conjugates in human ovarian cancer NIH: OVCAR-3 cells

Zinc oxide (ZnO) nanoparticles conjugated to porphyrin (ZnO-MTAP) have been designed, synthesized and evaluated for photodynamic therapy (PDT) against ovarian cancer. Based on the self-lighting photodynamic therapy (SLPDT) concept, photoactivation of ZnO-MTAP conjugates will lead to release of reactive oxygen species which, if effectively targeted to tumor cells, can elicit selective cytotoxicity. Following synthesis, conjugated nanoparticles were purified using gel exclusion chromatography and tumoricidal activity was evaluated using the human ovarian cancer cell line, NIH: OVCAR-3. Conjugates generated reactive oxygen species (ROS) in a concentration- and illumination-dependent manner following exposure to ultraviolet A light (365 nm). Cellular uptake of nanoparticle conjugates was detected using laser scanning confocal microscopy. Under dark conditions, ZnO-MTAP conjugates (1-10 μM, 24 hr) exhibited little cytotoxic potential. Ultraviolet radiation alone (UVA, 9 kJ/m²) also had little effect on cell viability. Co-exposure to both UVA radiation (9 kJ/m²) and ZnO nanoparticle conjugates however, elicited concentration-dependent cytotoxicity (40% and 92%, respectively). Furthermore, caspase 3/7 activity was markedly elevated 3-6 hours after irradiation, suggesting apoptosis was induced by the phototherapy. These findings provide proof-of-concept that photoactivation of ZnO-MTAP conjugates can be useful for targeted destruction of tumor cells.