From Barrier to Gateway: Nanomaterials Reshaping the Tumor Microenvironment for Therapy.

The tumor microenvironment constitutes the external condition that supports the survival and development of tumor cells. It promotes tumor cell proliferation and survival by secreting various cytokines and the provision of nutritional support, thereby driving tumor advancement. However, its structural density and complex composition pose significant barriers to drug delivery and therapeutic intervention, necessitating the development of advanced techniques for effective penetration. In recent years, nanotechnology, characterized by its distinctive physicochemical properties and excellent targeting and regulatory capabilities, has shown tremendous potential in overcoming the tumor microenvironment barriers, garnering significant research interest. This paper systematically summarizes the formation mechanisms of various TME subtypes, including immunosuppressive, metabolic, acidic, hypoxic, stromal, mechanical, microbial, inflammatory, and neural TME. It analyzes the principal challenges faced by nanomaterials in regulating these microenvironments, focuses on research strategies and application prospects of nanomaterials across different subtype microenvironments, and proposes novel directions for future investigation. The objective is to facilitate breakthroughs in the translational application of nanomaterials from mechanistic innovation to clinical practice.