MiRNA-204-5p and Oxaliplatin-loaded silica nanoparticles for enhanced tumor suppression effect in CD44-overexpressed colon adenocarcinoma

In this study, we have successfully formulated oxaliplatin (OXL) and miRNA-204-5p loaded polyethyleneimine (PEI)/hyaluronic acid (HA)-assembled mesoporous silica nanoparticles (OXmi-HSMN). Our study, for the first time, proved that miRNA-204-5p can generate a synergistic anticancer effect with OXL with HMSN, and thus improve the effects of therapeutic efficacy in colon cancers. In vitro targeting studies showed that OXmi-HSMN exhibited higher uptake efficiency in CD44 receptor over-expressed HT-29 cells via CD44 receptor-mediated endocytosis. OXmi-HMSN exhibited a higher cell cytotoxicity compared to any other formulations indicating that internalization via CD44 receptor-mediated endocytosis increased the anticancer effect. The OXmi-HMSN showed significantly higher pre-apoptotic cells (43.9%) with significant apoptosis fractions (upper right quadrant - 20%) indicating the superior anticancer efficacy in terms of apoptosis inducing potentials. Importantly, OXmi-HMSN caused conspicuous inhibition of tumor growth and was significantly greater than that of either OXL or OXL-MSN (p<0.0001). OXmi-HMSN showed 30% of TUNEL positive cells compared to 8% TUNEL positive cells for free OXL and 6% for free miRNA-204-5p treated group indicating the wide spread apoptosis of cells throughout the tissue section. Current study provides a delivery platform for dual therapeutics for enhanced therapeutic efficacy in the management of colon cancer.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research