Multi-sensitive functionalized niosomal nanocarriers for controllable gene delivery in vitro and in vivo
Najmeh Alsadat Abtahi, Saba Salehi, Seyed Morteza Naghib, Fatemeh Haghiralsadat, Mohammadmahdi Akbari Edgahi, Sadegh Ghorbanzadeh, Wei Zhang
Abstract
Abstract MicroRNAs, 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