Biocompatible 2D Cu-TCPP Nanosheets Derived from Cu2O Nanocubes as Multifunctional Nanoplatforms for Combined Anticancer Therapy

Two-dimensional (2D) metal-organic frameworks (MOFs) could serve as multifunctional nanoplatforms to load small-molecule drugs and enzyme-mimicking nanoparticles (NPs) with a high efficiency for combined cancer therapy. Herein, we have prepared novel 2D Cu-tetrakis (4-carboxyphenyl) porphyrin (TCPP) nanosheets with an average thickness of 1.2 ± 0.1 nm using Cu₂O nanocubes (50 nm) as a template and solid copper ion supplier. Cu₂O nanocubes can be consumed and hybridized with the obtained Cu-TCPP, depending on the molar ratio of Cu₂O and TCPP linker. The resultant Cu₂O/Cu-TCPP could serve as nanoplatforms for co-loading of Pt and Au NPs to construct multifunctional Cu₂O/Cu-TCPP/(Pt-Au) nanomedicines, which showed a superior anticancer effect via multiple therapeutic modes. For instance, Cu(II)-TCPP can produce ¹O₂ in the presence of acidic H₂O₂ by the Russell mechanism and the intrinsic Cu(I) ions (derived from the residual Cu₂O) could mediate a Fenton-like reaction in tumorous tissues to generate toxic hydroxyl radicals (•OH). Moreover, the loaded Pt NPs with catalase (CAT)-mimic activity could decompose hydrogen peroxide (H₂O₂) into O₂ within the tumor cells, increasing the local O₂ concentration, modulating the tumorous hypoxia atmosphere, and promoting the O₂-dependent glucose oxidation reaction. Furthermore, Au NPs with glucose oxidase (GOx)-mimic activity could accelerate the consumption of glucose and cut nutrient supply to induce starvation therapy. Consequently, our designed 2D MOF-based therapeutic nanomedicines would be a promising candidate for future smart and combined cancer therapy.