Hybrid Nanocomposite of Imidazolium Based Chitosan and Anderson-type Manganese Polyoxomolybdate for Boosting Drug Delivery Against Breast Cancer

Abstract Polyoxometalates (POMs) are a class of inorganic cytotoxic agents with potential anticancer effects. As the nano-formulation is one of the best approaches to adjust the therapeutic effects along with selective delivery, in this study, a novel biocompatible nano-composite (NC) of Anderson-type manganese polyoxomolybdate (MnMo6) was prepared using chitosan conjugate to achieve better selective cytotoxicity profile.Imidazolium modified chitosan (CSIm) was utilizedto getthe MnMo6 hybridNCs (MnMo6@CSIm NCs).The best resulting NCs were evaluated for their anticancer activity against breast cancer cell lines (MCF-7 & MDA-MB-231) as well as HUVEC normal cells using MTT assay. Furthermore, cellular uptake, apoptosis ratio and cell migration inhibition were evaluated on the MDA-MB-231 cell line as the triple-negative aggressive cell line.The optimized NPs had a zeta potential above +27 mV with a uniform distribution of sizes around 145 nm. The loading content and release efficiency were both satisfying (about 44% and 98%). In the release study, a pH-responsive release was detectedcomparing the neutral conditions.The NCs had a better anticancer activity than free MnMo6 in both cancer cell lines, without detectable cytotoxicity against HUVEC normal cells. The cellular uptake was about 100 %, and apoptosis value was enough high (81%) compared to free MnMo6. Interestingly, the MnMo6 hybrid NCs inhibitedthe cell migration of MDA-MB-231 cell line1.5 times better than the free MnMo6. All of these results are fascinating to follow more pre-clinical studies on this hybrid NC.