miR-542-3p Appended Sorafenib/All-trans Retinoic Acid (ATRA)-Loaded Lipid Nanoparticles to Enhance the Anticancer Efficacy in Gastric Cancers

Abstract

Purpose: In this study, miR-542-3p appended SRF/ATRA-loaded solid lipid nanoparticle was successfully prepared and demonstrated for its therapeutic efficacy against gastric cancers.

Methods: The particles were nanosized and typically spherical in shape. In vitro release study showed that release of ATRA was significantly slower compared to that of SRF from the NPs.

Results: MTT assay showed that miR-542-3p have a strong inhibitory effect on the proliferation of MGC-803 cancer cells in a typical dose dependent manner. Nanocarrier encapsulation of SRF + ATRA induced a significantly higher cytotoxic effect compared to either individual drug or cocktail combinations indicating that the cellular uptake of different formulations was rate limiting factor in the therapeutic efficacy. Importantly, miR-542-3p-based miSRNP exhibited an extremely significant toxic effect compared to any other treated group. Importantly, miSRNP induced a significantly higher early (~55%) and late (~15%) apoptotic effect in gastric cancer cells. In vivo anticancer analysis results clearly suggest that nanoparticle encapsulation of combination of SRF and miRNA (with miRNA) will have greater antitumor efficacy in tumor mice.

Conclusion: Overall, unique combination of miRNA coupled with SRF + ATRA in a lipid nanocarrier could be a promising therapeutic approach in gastric cancer treatment.

Keywords: all-trans retinoic acid (ATRA); apoptosis; gastric cancer; miRNA; solid lipid nanoparticles; sorafenib.