Au-reinforced chemo-photodynamic therapy of lanthanide-doped nanoplatforms with upconversion-downshifting luminescence via catalytic amplification

Abstract

The vast majority of lanthanide-doped nanoparticles (LnNPs) exhibit a single mode of upconversion luminescence (UCL) or downshifting luminescence (DSL) for photodynamic therapy (PDT) or diagnostic imaging of tumors, respectively. In order to achieve both UCL and DSL, it is often necessary to dope the luminescent ions in different shell layers to prevent their luminescence quenching, resulting in tedious synthesis steps. Herein, upconversion-downshifting nanoparticles (UDNPs) co-doped with Er³⁺ and Ho³⁺ enable the simultaneous dual-wavelength DSL for in vivo near-infrared (NIR)-II fluorescence imaging of tumors. On the other hand, the UCL of UDNPs could activate merocyanine photosensitizers (MC 540), resulting in the generation of reactive oxygen species (ROS) and the achievement of PDT. Importantly, Au NPs with glucose oxidase-like properties could consume glucose and promote H₂O₂ accumulation in tumor cells. Au-catalyzed UDNPs modified with Fe-tannic acid (FeTA) (UDNP-MC/Au-FeTA) could not only enhance the effect of PDT but also realize chemodynamic therapy (CDT) by reacting with Fe²⁺ generated from slightly acidic decomposition of FeTA to accelerate hydroxyl radical (^•OH) generation. The combination of long- and short-acting dual-dynamic therapy could mutually reinforce and compensate for the lack of therapeutic efficacy resulting from luminescence quenching caused by co-doping luminescent ions. Therefore, UDNP-MC/Au-FeTA guided by NIR-II fluorescence imaging could achieve efficient synergistic dual-dynamic therapy of tumors through differentially expressed genes associated with apoptosis and oxidative stress-related pathways. NIR-II fluorescence imaging diagnostic and dual-dynamic therapeutic strategy, which employs Au-catalyzed lanthanide co-doped UDNPs represents a dexterous design concept for promising anti-tumor applications.