Breast cancer is a major health problem that affects millions of women worldwide. It is caused by the abnormal growth and invasion of breast cells, which can metastasize to other organs and tissues [1]. The molecular mechanisms of breast cancer are complex and involve multiple signaling pathways that regulate various cellular functions, such as survival, proliferation, differentiation, apoptosis, migration, and invasion [2]. Among these pathways, the mitogen-activated protein kinase (MAPK) [3] and the bone morphogenetic protein (BMP) [4] pathways play important roles in breast cancer development and progression. Therefore, targeting these pathways could be a potential strategy for breast cancer treatment.
MicroRNAs (miRNAs) have been shown to act as key regulators of various signaling pathways, including the MAPK and BMP pathways, in breast cancer [4, 5]. One of the miRNAs that has been implicated in breast cancer is miR-125b, which can suppress the expression of several oncogenes, such as Raf-1 and BMPR1b [6, 7]. Raf-1 is a crucial component of the MAPK pathway, which stimulates cell survival and proliferation [8]. BMPR1b is a type I receptor of the BMP pathway, which enhances cell migration and invasion [9]. Thus, restoring the expression of miR-125b in breast cancer cells could inhibit the MAPK and BMP pathways and reduce their malignant properties.
However, the delivery of miR-125b to breast cancer cells faces several challenges, such as low stability, low cellular uptake, and low target specificity [10]. To overcome these challenges, an efficient and safe delivery system for miR-125b is needed. One of the possible delivery systems is chitosan/miR-125b nanoparticle, which is a complex of chitosan and miR-125b at the nanoscale [11]. Chitosan is a natural polysaccharide derived from the shells of crustaceans, such as shrimp and crab. It has many advantages as a delivery carrier, such as biocompatibility, biodegradability, low toxicity, high stability, and mucoadhesiveness [12]. Chitosan can also protect miR-125Chitosan can form nanoparticles with miRNAs through electrostatic interactions and protect them from nuclease degradation. Chitosan can enhance the cellular uptake and target specificity of miRNAs by modifying its surface with functional groups or ligands [13, 14].
Several studies have reported the use of chitosan nanoparticles (CNPs) for miRNA delivery in different models of cancer. For example, Denizli et al. (2017) developed chitosan nanoparticles for the delivery of miR-34a, a tumor suppressor miRNA, to prostate cancer cells and tumors. They showed that chitosan nanoparticles could efficiently deliver miR-34a and inhibit the expression of its target genes, such as BCL2 and MET. They also demonstrated that chitosan nanoparticles could suppress tumor growth and metastasis in a mouse model of prostate cancer [14]. Similarly, Deng et al. (2014) synthesized hyaluronic acid-chitosan nanoparticles for the co-delivery of miR-34a and doxorubicin, a chemotherapeutic drug, to triple negative breast cancer cells and tumors. They showed that hyaluronic acid-chitosan nanoparticles could enhance the cellular uptake and intracellular release of miR-34a and doxorubicin, and induce synergistic effects on apoptosis and cell cycle arrest. They also showed that hyaluronic acid-chitosan nanoparticles could improve the antitumor efficacy and reduce the systemic toxicity of doxorubicin in a mouse model of breast cancer [15].
Other studies have explored the use of CNPs for miRNA delivery in non-cancer models. For instance, Su et al. (2020) fabricated chitosan hydrogel doped with PEG-PLA nanoparticles for the local delivery of miR-146a, an anti-inflammatory miRNA, to treat allergic rhinitis. They showed that chitosan hydrogel could provide sustained release of miR-146a and PEG-PLA nanoparticles could facilitate the intracellular delivery of miR-146a. They also showed that chitosan hydrogel could reduce the nasal symptoms and inflammation in a mouse model of allergic rhinitis [11]. Likewise, Wu et al. (2020) designed chitosan-miRNA functionalized microporous titanium oxide surfaces for the delivery of miR-21, an osteogenic miRNA, to enhance the osteogenic activity of titanium implants. They showed that chitosan-miRNA functionalized surfaces could increase the adhesion, proliferation, and differentiation of osteoblasts, and upregulate the expression of osteogenic genes, such as ALP, RUNX2, and OCN [16].
These studies demonstrate the potential of CNPs for miRNA delivery in various diseases. However, there are still some limitations and challenges that need to be addressed, such as the optimization of chitosan properties, the improvement of miRNA loading efficiency and stability, the modulation of miRNA release kinetics and biodistribution, the evaluation of immunogenicity and biotoxicity, and the validation of therapeutic efficacy and safety in clinical trials. Therefore, further research and development are needed to advance the field of chitosan nanoparticles for miRNA delivery and to translate this promising strategy into clinical applications.
The aim of this study was to investigate the anti-cancer effect of chitosan/miRNA-125b nanoparticles on breast cancer cells (MCF-7). The study examined how the nanoparticles influenced the cell growth and the expression of two genes (Raf-1 and BMPR1b) that are involved in important cell signaling pathways. The study compared the CNPs with free microRNA125b, and used various in vitro methods to measure the cell and gene responses. The study explored the potential of the CNPs as a novel therapeutic agent for breast cancer.