Multi-sensitive functionalized niosomal nanocarriers for controllable gene delivery in vitro and in vivo

Abstract

AbstractMicroRNAs, which can contribute to numerous cellular functions through post-transcriptional silencing, have become well-documented candidates for cancer treatment applications, particularly in chemo-resistant cancers. Herein, several formulations were examined to optimize the essential parameters, and the niosomal formulation consisting of cholesterol:tween-80:DOTAP:PEG with 9:69:15:7 ratio had the best physicochemical parameters including spherical shape, high entrapment efficiency, small diameter (81 ± 0.65 nm), and appropriate positive charge (23 ± 0.64 mV). Here, we aimed to design a system with increased delivery efficiency which was tested by the encapsulation of miR-34a within niosome NPs and assessed the nano-niosomal delivery of miR-34a as a tumor suppressor in MCF-7 human adenocarcinoma cells. The results showed that our novel niosome systems with non-ionic surfactants can successfully eliminate cancer cells by increasing the expression of p53 and reducing the expression of NF-κB. In comparison with the free dispersion of miR-34a, the lysis of a nano-sized delivery system demonstrated a better cytotoxicity effect against cancer cells. Similar results were obtained by performing in vivo test on the 4T1 xenografted Balb/C mouse tumor model and the miR-34a-loaded niosomes displayed a better reduction in tumor size by improving approximately + 13% in tumor inhabitation rate while maintaining the bodyweight close to the first day. Therefore, it is concluded that miR-34a delivery via niosomes has high potential as a tumor suppressor and a reliable procedure for breast cancer treatment. Graphical Abstract