Reactive Oxygen Species -responsive release of tanshinone IIA for polycystic ovary syndrome treatment

Abstract Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder often associated with a chronic low-grade inflammatory state, which can elevate oxidative stress and exacerbate PCOS's pathophysiological processes. Natural anti-inflammatory herbal components have been employed for PCOS treatment; however, the challenge lies in effectively targeting these herbal active ingredients due to their poor solubility, low bioavailability, and multiple targets. In this study, we developed a reactive oxygen species (ROS)-sensitive herbal nanomedicine to facilitate the targeted release of active herbal ingredients to PCOS lesions. The herbal nanomedicine, designated MSN@Tan IIA-TK, was formulated by loading the anti-inflammatory herbal compound Tanshinone IIA (Tan IIA) into mesoporous silica nanoparticles (MSN) and grafting a ROS-responsive polymer, mPEG-TK-NHS, onto the surface. Our findings demonstrated that MSN@Tan IIA-TK released Tan IIA in response to elevated ROS levels in PCOS, subsequently reducing oxidative stress and inflammation while promoting the proliferation of ovarian granulosa cells. Further analyses indicated that MSN@Tan IIA-TK effectively mitigated endocrine dysfunction, inflammation, and ovarian damage by inhibiting the ferroptosis pathway. This study highlights the potential of innovative herbal nanomedicines targeting pathological environmental responses in PCOS treatment and offers new perspectives for the clinical application of other traditional herbal therapies.