All-in-One Theranostic Nanomedicine with Ultrabright Second Near-Infrared Emission for Tumor-Modulated Bioimaging and Chemodynamic/Photodynamic Therapy

Reactive oxygen species (ROS)-based therapeutic modalities including chemodynamic therapy (CDT) and photodynamic therapy (PDT) hold great promise for conquering malignant tumors. However, these two methods tend to be restricted by the overexpressed glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Here, we develop biodegradable copper/manganese silicate nanosphere (CMSN)-coated lanthanide-doped nanoparticles (LDNPs) for trimodal imaging-guided CDT/PDT synergistic therapy. The tridoped Yb3+/Er3+/Tm3+ in the ultrasmall core and the optimal Yb3+/Ce3+ doping in the shell enable the ultrabright dual-mode upconversion (UC) and downconversion (DC) emissions of LDNPs under near-infrared (NIR) laser excitation. The luminescence in the second near-infrared (NIR-II, 1000-1700 nm) window offers deep-tissue penetration, high spatial resolution, and reduced autofluorescence when used for optical imaging. Significantly, the CMSNs are capable of relieving the hypoxic TME through decomposing H2O2 to produce O2, which can react with the sample to generate 1O2 upon excitation of UC photons (PDT). The GSH-triggered degradation of CMSNs results in the release of Fenton-like Mn2+ and Cu+ ions for •OH generation (CDT); simultaneously, the released Mn2+ ions couple with NIR-II luminescence imaging, computed tomography (CT) imaging, and magnetic resonance (MR) imaging of LDNPs, performing a TME-amplified trimodal effect. In such a nanomedicine, the TME modulation, bimetallic silicate photosensitizer, Fenton-like nanocatalyst, and NIR-II/MR/CT contrast agent were achieved "one for all", thereby realizing highly efficient tumor theranostics.