Research progress on precision targeted therapy strategies for breast cancer based on tumor microenvironment.

The tumor microenvironment (TME) plays a crucial role in the progression of BC, characterized by abnormal pH, aberrant enzyme expression, redox imbalance, etc. Nano-drug delivery systems (NDDSs) responsive to TME have emerged, including pH-responsive, enzyme-responsive, redox-responsive, and multi-responsive intelligent cascading systems. These systems effectively address tumor heterogeneity by improving intratumoral drug distribution and penetration, thereby enhancing therapeutic specificity and safety. In the future, the development of multi-modal intelligent NDDS, the design of programmable responsive systems, AI-driven personalized nano-drugs, and interdisciplinary collaboration to promote clinical translation will become key research focuses. This review not only systematically elucidates the response mechanism characteristics of TME in BC, but also focuses on analyzing the special requirements of the unique extracellular matrix and subtype specificity of BC for nanomedicine design. Furthermore, it summarizes the development directions of TME-responsive nano-delivery systems for BC, providing new insights to enhance the precise targeted therapy of BC.