Abstract
Photomedicine, which utilizes light for therapeutic purposes, has several hurdles such as limited tissue penetration for short-wavelength light and inadequate deep tissue efficacy for long-wavelength light. Photon energy upconversion (UC) reveals promise in photomedicine because it enables the conversion of lower-energy photons into higher-energy photon. Lanthanide (Ln)-based inorganic UC system has been extensively studied but faces challenges, including high excitation laser power density, intrinsically subpar UC quantum efficiency, and potential biotoxicity. Recently, an organic-based triplet-triplet annihilation UC (TTA-UC) system has emerged as a novel UC system due to its prolonged emission lifetime upon low power laser excitation and exceptional UC quantum yield. In this study, we developed water-dispersible hyaluronic acid (HA)-conjugated polycaprolactone (PCL) nanoparticles loaded with TTA-UC chromophores (HA-PCL/UC NPs), which allow deeper tissue penetration by converting red light (635 nm) into blue light (470 nm) for noninvasive transdermal delivery. HA-PCL/UC NPs demonstrated a 1.6% high quantum yield in distilled water, improved cellular imaging in HeLa cells, and effectively penetrated the deep tissue of porcine skin, showing upconverted blue light. Our strategy holds significant potential as a next-generation noninvasive photomedicine platform for bioimaging, photo-triggered drug delivery, and photodynamic therapy, ultimately advancing targeted and effective therapeutic interventions.