Cu ₂ O-Coated Upconversion Nanoparticles Loaded on Ti ₃ C ₂ MXene for Multimodal Co-Catalytic Cancer Therapy

To overcome the intrinsic limitations of traditional oncologic interventions─namely, insufficient tumor accumulation via the enhanced permeability and retention (EPR) effect and the modest efficacy of single-modality treatments─there is an imperative to engineer an integrated, multifunctional theranostic nanoplatform. Here, we designed core–shell NaGdF 4:Yb,Tm@NaGdF 4:Yb, Nd upconversion nanoparticles (UCNPs) to suppress surface-associated quenching and to serve as a high-performance computed tomography (CT) imaging contrast agent. A conformal mesoporous SiO 2 (mSiO 2 ) shell was subsequently grafted, imparting amino surface chemistry, and furnishing high-capacity mesopores for controlled molecular loading. pH-responsive Cu 2 O nanocatalysts (∼3 nm) were anchored within the mSiO 2 matrix, enabling Fenton-like conversion of endogenous H 2 O 2 into cytotoxic •OH selectively within the acidic tumor microenvironment. Finally, two-dimensional Ti 3 C 2 MXene nanosheets were electrostatically assembled onto the exterior to exploit their exceptional NIR photothermal conversion (η ≈ 41.81% at 808 nm), thereby integrating photothermal (PTT), photodynamic (PDT), chemodynamic (CDT), and computed-tomography (CT) imaging modalities into a single construct. Experimental validation confirmed that UCNPs@mSiO 2 –Cu 2 O/Ti 3 C 2 elicits targeted hyperthermia (Δ T = 55 °C within 5 min) while maintaining hemocompatibility (<2% hemolysis) and negligible cytotoxicity toward normal cells. In orthotopic 4T1 murine models, multimodal therapy eradicated >90% of tumor burden without histopathological evidence of damage to heart, liver, spleen, lung, or kidney. This finding provides a feasible strategy for precision theranostic in which a single nanoplatform synchronizes real-time imaging with synergistic, tumor-selective multimodal ablation.