Mechanistic insight into nanomedicine for polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder. It is the most prevalent disease in reproductive-aged females worldwide. PCOS is characterized by hormonal imbalance, chronic anovulation, and metabolic dysfunction. The complex etiology of PCOS, which involves genetic, environmental, and lifestyle factors, contributes to the variability in its clinical presentation and complicates treatment strategies. Current therapeutic and disease management options, including hormonal therapy, and insulin sensitizers are limited by the side effects associated with non-targeted approach. In recent years, nanomedicine has emerged as a promising approach to overcome these challenges. It offers enhanced bioavailability, targeted drug delivery, and reduced systemic toxicity. Nanoparticles (NPs) possess unique physicochemical properties including high drug loading capacity and a large surface area. They can bind both hydrophilic and hydrophobic substances. These characteristics make NPs a promising platform for targeted and controlled drug delivery. Challenges such as off-target effects and limited efficacy in traditional therapy are mitigated when therapeutic agents are combined with nanoparticles, increasing precision and therapeutic outcomes. This review provides a comprehensive summary of the unique properties of nanoparticles that play crucial roles in their interactions with reproductive systems. Further we focus on the mechanistic insights into how nanoparticles modulate key PCOS-related pathways, including insulin signaling, steroidogenesis, inflammation and oxidative stress. This review highlights the role of some specific nanocarriers (e.g.; curcumin loaded NPs, selenium NPs, and exosomes) in restoring metabolic and reproductive functions in PCOS. In addition, we discuss NPs synthesis, delivery mechanisms, and their interactions at the molecular and cellular levels to PCOS pathology, with their putative role in pathway linked modulation of insulin resistance, hyperandrogenism, inflammation, and disrupted folliculogenesis. Understanding these mechanisms is essential for designing effective, nanomedicine for PCOS and possibly for other PCOS related chronic diseases.

Keywords: (PTEN)-dependent signaling pathways; Exosomes; Green synthesis; Inflammation; Insulin resistance; Nanomedicine; PI3K/Akt/mTOR; Polycystic ovary syndrome; Targeted drug delivery; microRNA.