Tumor-responsive nanomedicine based on Ce³⁺-modulated up-/downconversion dual-mode emission for NIR-II imaging-guided...

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) based on intratumoral generation of reactive oxygen species (ROS) have been playing crucial roles in conquering tumors. However, the above therapeutic methods are still constrained by the overexpressed tumor glutathione (GSH) and intrinsic tumor resistance to conventional organic photosensitizers. Herein, lanthanide-doped nanoparticles (LDNPs) were coated with inorganic bimetallic copper and manganese silicate nanospheres (CMSNs) and modified with sodium alginate (SA) for second near-infrared (NIR-II, 1000-1700 nm) imaging-guided CDT and PDT. Interestingly, cross-relaxation (CR) pathways between Ce³⁺ and Ho³⁺ and CR between Ce³⁺ and Er³⁺ are fully exploited to enable dual-mode upconversion (UC) and NIR-II downconversion (DC) emissions of LDNPs under 980 nm laser excitation. UC emission can induce CMSNs to produce toxic singlet oxygen (¹O₂) for PDT, and the released Mn²⁺ and Cu⁺ ions caused by GSH-induced degradation of CMSNs can react with endogenous H₂O₂ to produce hydroxyl radical (˙OH) for CDT. Significantly, the ultrabright NIR-II DC emission endows the systems with exceptional optical imaging capabilities. All results affirm the potency of such an "all in one" theranostic nanomedicine integrating PDT, CDT and remarkable NIR-II imaging abilities accompanied by the function of modulating tumor microenvironment in cancer theranostics.