Ultrathin Porous Nitrogen-Doped Carbon-Coated CuSe Heterostructures for Combination Cancer Therapy of Photothermal Therapy, Photocatalytic Therapy, and Logic-Gated Chemotherapy

The construction of nanoplatforms for the multi -modal cancer therapy still remains an enormous challenge. Ultrathin porous nitrogen-doped carbon coated stoichiometric copper selenide heterostructures (CuSe/NC) are prepared using a facile and green one-pot hydrothermal method. Interestingly, CuSe/NC itself can achieve both photothermal therapy (PTT) and photocatalytic therapy (PCT) under irradiation of a single near-infrared (NIR) light (808 nm), which is convenient and safe for clinical applications. Importantly, the triple-enhanced NIR light-activated PCT, including O2-independent free radicals, Fenton-like reaction, and glutathione (GSH) depletion, breaks through the limitations of hypoxia and overexpressed GSH in cancer cells. Furthermore, CuSe/NC is loaded with doxorubicin (DOX) via metal coordination and then decorates with DNA to construct the CuSe/NC-DOX-DNA nanoplatform. Surprisingly, the facile nanoplatform has an advanced biocomputing capability of an AND Boolean logic gate with the smart AND logic controlled release of DOX upon combined stimuli of pH and GSH for precise cancer chemotherapy. The synergistic mechanism of proton-mediated ligand exchange between DOX and GSH is proposed for the AND logic controlled drug release from CuSe/NC-DOX-DNA. In vitro and in vivo studies demonstrate that CuSe/NC-DOX-DNA has excellent anticancer efficacy and negligible toxicity. This innovative nanoplatform with multienhanced anticancer efficacy provides a paradigm for combination cancer therapy of PTT, PCT, and chemotherapy.

Automated summary

The construction of ultrathin porous nitrogen-doped carbon coated stoichiometric copper selenide heterostructures (CuSe/NC) for multi-modal cancer therapy is challenging. These nanoplatforms can achieve both photothermal therapy (PTT) and photocatalytic therapy (PCT) under a single near-infrared (NIR) light, and can be loaded with doxorubicin (DOX) and DNA to enable smart release for precise chemotherapy. In vitro and in vivo studies confirm the excellent anticancer efficacy and negligible toxicity of CuSe/NC-DOX-DNA nanoplatform, providing a paradigm for combination cancer therapy.