Salidroside-Based Nanomedicines for Triple-Negative Breast Cancer: From Molecular Mechanisms to Clinical Translation.

Triple-negative breast cancer (TNBC) presents a substantial therapeutic challenge due to its aggressive biological characteristics and the absence of actionable molecular targets. Salidroside, the principal bioactive compound of Rhodiola rosea, demonstrates significant anticancer potential; however, its clinical application is severely constrained by poor bioavailability (less than 12%) and a short half-life (2.3 hours). This review contributes to the field in three key ways. Firstly, it systematically elucidates the molecular mechanisms of salidroside in TNBC, emphasizing its distinctive dual role in redox homeostasis: inducing ferroptosis in cancer cells while safeguarding normal tissues. Secondly, it critically assesses advanced nanomedicine strategies such as PLGA-PEG nanoparticles, lipid-polymer hybrid nanoparticles, and biomimetic RBC membrane-camouflaged carriers-designed to address pharmacokinetic limitations. Thirdly, and most importantly, it proposes a biomarker-driven framework, centered on BRCA1 methylation and HIF-1α, along with a three-phase translational roadmap to advance salidroside into a precision nanomedicine for TNBC.