ConspectusPhototherapy including optogenetics, photodynamic therapy (PDT), photothermal therapy (PTT), and photoimmunotherapy (PIT) has been proven to be effective against different diseases. However, as the name suggests, phototherapy requires light irradiation, thus its therapeutic efficiency is often restricted by limited depth of light penetration within biological tissue. This light penetration limitation is significantly adverse to PDT and optogenetics because both therapies are usually activated with UV and visible light of very poor tissue penetration efficiency. Current light delivery methods usually involve cumbersome setups and require optical fiber or catheter insertion, which not only restrict the movement of patients but also impose incompatibility issues with chronic implantation. To address the existing challenges, wireless phototherapy was developed through various approaches over recent years, which usually relies on implantable wireless electronic devices. However, the application of wireless electronic devices is limited by invasion during implantation, unwanted heat generation, and adverse immunogenicity of these devices.Over the recent years, applying light conversion nanomaterials as light transducers for wireless phototherapy has garnered much interest. Compared with implantable electronic devices and optical fiber, nanomaterials can be easily injected into the body with minimal invasiveness and can also be surface functionalized to increase their biocompatibility and cell accumulation efficiency. Commonly applied light conversion nanomaterials include upconversion nanoparticles (UCNPs), X-ray nanoscintillators, and persistent luminescence nanoparticles (PLNPs). UCNPs and X-ray nanoscintillators can respectively convert near-infrared (NIR) light and X-ray, which have good tissue penetration efficiency, to UV or visible light, which is suitable for activating phototherapy. PLNPs can be excited by external light such as X-rays and NIR light and retain long afterglow luminescence after the removal of the excitation light source. As a result, applying PLNPs in phototherapy can potentially reduce irradiation time from external light sources, thus minimizing tissue photodamage. This Account aims to briefly discuss (i) the mechanisms of different phototherapies, (ii) the development and mechanisms of light conversion nanomaterials, (iii) the application of light conversion nanomaterials in wireless phototherapy, highlighting how they relieve current challenges in phototherapy, and (iv) perspectives for future development of light conversion nanomaterials for wireless phototherapy.
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