Near-Infrared Light-Responsive Upconversion Nanoparticles Supported Elemental Selenium for Combination Tumor Therapy: Selenium Therapy, Photocatalytic Therapy, and "AND" Logic-Gated Chemotherapy.

Multimodal tumor therapy based on "all-in-one" nanoplatforms enhances therapeutic efficacy, simplifies the construction process, and improves material utilization. Elemental selenium was successfully supported on upconversion nanoparticles (UCNPs) to constitute the near-infrared (NIR) light-responsive UCNP@Se heterostructures for the first time. Under 980 nm irradiation, the UCNP@Se heterostructures could not only produce holes and superoxide radicals •O but also catalyze the generation of hydroxyl radicals •OH by highly elevated levels of HO in tumor cells to kill the tumor cells. In addition to the superior photocatalytic performance, elemental selenium itself also exhibited inherent inhibition activity against tumor cells. On the basis of the binding of anthracycline anticancer drugs such as doxorubicin (DOX) to the supported elemental selenium through Cu bridging coordination, the UCNP@Se-Cu-DOX drug delivery system was constructed. The introduction of Cu not only improved the efficient loading of DOX but also achieved the "AND" logic-controlled release of DOX under the combined stimuli of low pH and overexpressed glutathione (GSH) in tumor cells. Moreover, the loaded Cu reacted with the overexpressed GSH to generate the active species Cu-GSSG upon NIR light irradiation, which further promoted tumor cell apoptosis. The NIR light-responsive UCNP@Se-Cu-DOX drug delivery system achieved the combination tumor therapy of selenium therapy, photocatalytic therapy, and logic-gated chemotherapy and has great potential applications in tumor therapy.