Facile-synthesized ultrasmall CuS nanocrystals as drug nanocarriers for highly effective chemo–photothermal combination therapy of cancer

Abstract

Combinational chemo–photothermal therapy has been considered as a promising strategy to enhance antitumor efficiency via synergistic effects for cancer treatments. Here, we have developed a smart ‘all-in-one’ platform that conveniently combined chemo- and photothermal therapies based on ultrasmall CuS NCs, which were synthesized using a facile, low cost, and water solution reaction method. Doxorubicin (Dox)-loaded CuS drug nanocarriers (CuS–Dox) were fabricated with loading capacity up to 21%. The resulting CuS–Dox exhibited pH and NIR light dual-responsiveness, demonstrating remarkably promoted Dox release in a weakly acidic environment in cancer cells and enhanced intercellular uptake under 808 nm laser irradiation. Based on in vitro cell cytotoxicity, the CuS–Dox endow excellent chemo–photothermal synergistic effects for cancer cell death or apoptosis, attributed to both the cytotoxicity of light-triggered Dox release and CuS-mediated photothermal ablation. More importantly, in vivo treatment has achieved the complete inhibition of tumor growth in 4T1-bearing mice under a low laser power density of 1.0 W cm⁻². These results demonstrate a better anti-tumor therapeutic efficacy of combined treatment in vitro and in vivo in comparison with chemotherapy or photothermal therapy alone. Our study highlights the promise of fabricating CuS–Dox drug nanocarriers for highly effective chemo–photothermal combination therapy of cancer.