Fe/Mn Bimetal-Doped ZIF-8-Coated Luminescent Nanoparticles with Up/Downconversion Dual-Mode Emission for Tumor Self-Enhanced NIR-II Imaging and Catalytic Therapy

ZIF-8, as an important photoresponsive metal-organic framework (MOF), holds great promise in the field of cancer theranostics owing to its versatile physiochemical properties. However, its photocatalytic anticancer application is still restricted because of the wide bandgap and specific response to ultraviolet light. Herein, we developed lanthanide-doped nanoparticles (LDNPs) coated with Fe/Mn bimetal-doped ZIF-8 (LDNPs@Fe/Mn-ZIF-8) for second near-infrared (NIR-II) imaging-guided synergistic photodynamic/chemodynamic therapy (PDT/CDT). The LDNPs were synthesized by encapsulating an optimal Yb3+/Ce3+-doped active shell on the NaErF4:Tm core to achieve dual-mode red upconversion (UC) and NIR-II downconversion (DC) emission upon NIR laser irradiation. At the optimal doping concentration, the UC and DC NIR-II emission intensities of LDNPs were increased 30.2- and 13.2-fold above those of core nanoparticles, which endowed LDNPs@Fe/Mn-ZIF-8 with an outstanding capability to carry out UC-mediated PDT and NIR-II optical imaging. In addition, the dual doping of Fe2+/Mn2+ markedly decreased the bandgap of the ZIF-8 photosensitizer from 5.1 to 1.7 eV, expanding the excitation threshold of ZIF-8 to the visible light region (similar to 650 nm), which enabled Fe/Mn-ZIF-8 to be efficiently excited by UC photons to achieve photocatalytic-driven PDT. Furthermore, Fe2+/Mn2+ ions could be responsively released in the tumor microenvironment through degradation of Fe/Mn-ZIF-8, thereby producing hydroxyl radicals (center dot OH) by Fenton/Fenton-like reactions to realize CDT. Meanwhile, the degradation of Fe/Mn-ZIF-8 endowed the nanosystems with tumor self-enhanced NIR-II imaging function, providing precise guidance for CDT/PDT.