MnO2-shelled Doxorubicin/Curcumin nanoformulation for enhanced colorectal cancer chemo-immunotherapy

Abstract

Metallodrug platinum compounds are indispensable components in the current standard combination for colorectal cancer treatment yet with severe additional adverse effects compromising the clinical outcomes. Having tumor microenvironment modulation and immunostimulatory effect, bio-compatible manganese (Mn) materials hold great promise for developing alternate metallodrug combination treatments. In this research, a novel MnO2-shelled nanoplatform was constructed to load two FDA-approved anti-tumor drugs, i.e., immunomodulatory curcumin (Cur) and immunostimulatory doxorubicin (Dox) to achieve enhanced dual-chemotherapy of primary tumors and remarkable inhibition of distant colorectal tumors. The experimental results have shown that MnO2 efficiently enhanced Dox/Cur chemotherapy with significant primary tumor inhibition (81%) at very low dosages (5.0 and 1.0 mg/kg of Cur and Dox, respectively). Furthermore, the MnO2-assisted Dox/Cur chemotherapy promoted strong tumoricidal adaptive immune responses and overwhelmingly inhibited tumorigenesis in the tumor rechallenge experiment. This work has thus demonstrated the promising efficacy of the Mn/Dox/Cur nano-formulation and provided a novel way to improve immunostimulation of conventional chemotherapeutics using active metal oxide nanomaterials for colorectal cancer treatment.