Enzyme-Catalyzed Synthesis of Selenium-Doped Manganese Phosphate for Synergistic Therapy of Drug-Resisted Colorectal Tumor

Abstract

Abstract Postoperative chemotherapy for colorectal cancer often causes multidrug resistance (MDR), which seriously affects the therapeutic effect and has been an urgent problem to be solved. Herein, selenium-doped manganese phosphate (Se-MnP) nanoparticles with amorphous structure have been prepared by a bioinspired enzyme-catalyzed strategy, using alkaline phosphatase, fructose disodium diphosphate. Se-MnP have an organic-inorganic hybrid composition, which is assembled from smaller-scale nanoclusters. Se-MnP has showed good Fenton reaction activity in chemodynamic therapy (CDT) due to the presence of manganese ions. Moreover, results from in vitro and in vivo studies demonstrated that Se-MnP as an effective drug carrier of oxaliplatin (OX) can reverse multidrug resistance of colorectal cancer cells and simultaneously induce casparase-mediated apoptosis of colorectal cancer cells. The Se-MnP reverse the MDR of colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, the in vivo studies demonstrated that OX-loaded Se-MnP can significantly inhibit OX-resistant HCT116 (HCT116/DR) tumor growth in nude mice. Considering the facile method of preparation and biomimetic chemical properties, the Se-MnP with the multiple functions will be a promising candidate for treating colorectal tumors with MDR characteristics.