Inflammation Targeting Lymphocyte Apoptotic Body Hybrid Nanovesicles Alleviate Ovarian Inflammation in Polycystic Ovary Syndrome.

Abstract

Sustained inflammation localized in the ovarian microenvironment has been implicated as a key pathophysiological driver of polycystic ovary syndrome (PCOS), primarily disrupting normal folliculogenesis and arresting ovulation. Current therapies generally fail to address this underlying pathology due to their limitation in precisely targeting or modulating the ovarian immune microenvironment. Consequently, inflammation-induced tissue damage remains largely unresolved. To overcome this limitation, we developed a biomimetic hybrid nanovesicle termed TLAB@ATS. This platform combines anti-inflammatory T cell-derived apoptotic bodies (AB) with reactive oxygen species (ROS)-responsive thioketal (TK)-linked lipids for the targeted delivery of artesunate (ATS). Leveraging the natural homing ability of AB, TLAB@ATS specifically accumulates in ovarian inflammation, where elevated ROS levels induce cleavage of the TK linkers to trigger the on-demand release of ATS. We found that TLAB@ATS suppresses the expression of pro-inflammatory cytokines, significantly reduces ovarian oxidative stress and inflammatory immune cell infiltration, and thereby restores endocrine balance, alleviates ovarian inflammatory infiltration, and promotes normal folliculogenesis. Collectively, this tailored nanoplatform provides a targeted approach for alleviating ovarian inflammation in PCOS.