Infrared light utilized for photodynamic therapy by activation of rare earth phosphors for visible light generation

摘要

Introduction: Photodynamic therapy (PDT) is a treatment for cancer requiring activation of a photosensitizer for light-mediated tumor cytotoxicity. PDT is limited by tissue penetration because visible light is required for photosensitizer activation. Sunstones~TM are rare-earth phosphors which up-convert energy from infrared wavelengths to emit higher energy in the visible spectrum. We utilized this unique characteristic to generate light of appropriate intensity and wavelength for photosensitizer activation and subsequent tumor cell eradication. Methods: Sunstones~TM with infrared absorption at 808 and 980nm and visible two-photon emission at 549.9 and 663.lnm were used. A murine NSCLC line was used to determine in vitro toxicity of Sunstones~TM and dose response curves for Sunstones~TM-mediated PDT. Human NSCLC cells were incubated with/without Photofrin~TM (photosensitizer). Experimental groups included: Infrared light treatment (IR), IR+Photofrin~TM, IR+Sunstones~TM, and IR+Sunstones~TM+Photofrin~TM. Groups were exposed to 2.5W of 808nm light and assayed for metabolic activity.Results: In vitro toxicity assays showed no significant toxicological side effects after 1 week incubation with Sunstones~TM and demonstrated linear response in cytotoxicity as treatment times and infrared dose increased. IR+Sunstones~TM+Photofrin~TM group showed significantly decreased metabolic activity compared to control cells, cells treated with IR+Sunstones~TM, and IR alone.Conclusion: Sunstones~TM are nontoxic nanocrystals capable of activating photosensitizers for PDT. Future directions include conjugation of up-converters to a novel photosensitizer and managing the selective uptake of conjugate by tumor cells.