In photodynamic therapy, light is absorbed by a therapy agent (photosensitizer) to generate reactive oxygen, which then locally kills diseased cells. Here, we report a new form of photodynamic therapy in which nonlinear optical interactions of near-infrared laser radiation with a biological medium in situ produce light that falls within the absorption band of the photosensitizer. The use of near-infrared radiation, followed by upconversion to visible or ultraviolet light, provides deep tissue penetration, thus overcoming a major hurdle in treatment. By modelling and experiment, we demonstrate activation of a known photosensitizer, chlorin e6, by in situ nonlinear optical upconversion of near-infrared laser radiation using second-harmonic generation in collagen and four-wave mixing, including coherent anti-Stokes Raman scattering, produced by cellular biomolecules. The introduction of coherent anti-Stokes Raman scattering/four-wave mixing to photodynamic therapy in vitro increases the efficiency by a factor of two compared to two-photon photodynamic therapy alone, while second-harmonic generation provides a fivefold increase.
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This work was supported in part by a grant from the Air Force Office of Scientific Research (grants no. 1096313-1-58130 and no. FA95500610398). J.Q. acknowledges support from the National Natural Science Foundation of China (61378091) and the National Basic Research Program of China (grant no. 2012CB825802).
The authors declare no competing financial interests.
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Kachynski, A., Pliss, A., Kuzmin, A. et al. Photodynamic therapy by in situ nonlinear photon conversion. Nature Photon 8, 455–461 (2014). https://doi.org/10.1038/nphoton.2014.90
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