Near-infrared light-induced self-assembled lanthanide nanoparticles for boosted radiosensitization and persistent tumor therapy monitoring

Cancer radiotherapy resistance is a significant barrier to achieving optimal radiotherapy outcomes, prompting the continuous emergence of radiation sensitizing agents. To enhance the retention of radiosensitizers at tumor sites and thereby amplify their radiosensitizing effects, a novel nanoparticle aggregation platform (DH&UH NPs) responsive to second near-infrared light was developed, integrating radiosensitization and biological imaging functionalities. The platform is comprised of hyaluronic acid derivatives modified lanthanide-doped down-conversion nanoparticles (DH NPs) and lanthanide-doped upconversion nanoparticles (UH NPs). Under 980 nm laser irradiation, UH NPs efficiently generate UV light, which induces a tramsformation of the hydroxyl groups on the surface-bound NB molecules of the UH NPs into aldehyde groups. The aldehyde groups would react with the amino groups on UH NPs and the hydrazine groups of DH NPs, forming stable nanoparticle aggregates. This innovative design not only prolongs the duration of tumor imaging but also ensures sustained retention of the radiosensitizer at the tumor site. Furthermore, the organic diselenide bond in HA derivatives, serving as a radiosensitizer, generated abundant reactive oxygen species under X-ray radiation, thereby significantly enhancing the radiosensitization effect. Therefore, this innovative approach holds great promise as a versatile tool for long-term tumor imaging and achieving ideal radiation therapy effects.