Kai Huang, PhD
Department of Biochemistry and Molecular Biotechnology
University of Massachusetts Chan Medical School
Abstract: Biophotonics has been widely applied as versatile and powerful approaches for biomedical applications, such as for bioimaging, biodetection, photodynamic therapy, and optogenetics. However, conventional biophotonics suffers from several constraints. For example, the short-wavelength excitation light cannot penetrate deep into the tissue, thus requiring an invasive light delivery system for deep-tissue photodynamic therapy or optogenetics. In addition, luminescence signal is interfered with autofluorescence noise, bringing difficulties for high-quality bioimaging and biodetection. Here, we address these issues by developing unconventional nanobiophotonics, where we apply upconversion or persistent luminescence nanoparticles for anti-cancer therapy. Upconversion nanoparticles (UCNPs) convert near-infrared (NIR) excitation into short-wavelength visible light emission and thus serve as the light-transducer to bring deep tissue penetration NIR excitation for wireless photoactivations. We applied versatile nanoengineering approaches to produce UCNPs with controllable size/morphology, tunable and enhanced luminescence, and desirable biofunctionalizations. These UCNPs were applied for NIR-optogenetic control of CAR-T cell immunotherapy. We demonstrated that by wirelessly and spatiotemporally controlling the CAR-T cell activity, we can achieve effective and safer immunotherapy of cancer, overcoming the safety issue of conventional CAR-T immunotherapy. Persistent luminescence nanoparticles (PLNPs) are unique nanomaterials that emit long-lasting afterglow after excitation stops. PLNPs are significant for bioimaging by avoiding the autofluorescence induced by real-time excitation. We have developed the bottom-up syntheses of PLNPs with fine control of their energy traps, heterostructures, and energy accepting from dye-sensitizations, contributing to enhanced persistent luminescence. We have demonstrated that PLNPs with enhanced luminescence are excellent for ultrasensitive imaging-guided tumor surgery. In addition, we also demonstrated that by developing X-ray-excitable PLNPs, we can achieve X-ray-photodynamic therapy with limitless tissue penetration and enhanced tumor eradication.