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

Metallodrug platinum compounds are indispensable components in the current standard combination for colorectal cancer treatment yet with severe additional adverse effects compromising the clinical out-comes. Having tumor microenvironment modulation and immunostimulatory effect, bio-compatible manganese (Mn) materials hold great promise for developing alternate metallodrug combination treat-ments. 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 doxoru-bicin (Dox) to achieve enhanced dual-chemotherapy of primary tumors and remarkable inhibition of dis -tant 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 chemother-apeutics using active metal oxide nanomaterials for colorectal cancer treatment. (c) 2022 Elsevier Inc. All rights reserved.