Nanomedicines Reshape the Tumor Microenvironment: Multidimensional Strategies from Modulating “Barriers” to Metabolic Intervention

Abstract

Nanoparticle-driven remodeling of the Tumor Microenvironment (TME) represents a transformative strategy in cancer therapy, shifting from traditional approaches to multidimensional modulation. This review explores how engineered nanoparticles precisely target and alter key TME components—including immune cells (eg, NK cells, dendritic cells, T cells), cancer-associated fibroblasts, and the extracellular matrix—to overcome “Chemical barriers” and “physical barriers”. Furthermore, we highlight the pivotal role of nanoparticles in reprogramming TME metabolism, such as alleviating hypoxia, disrupting the Warburg effect, and modulating lipid and adenosine metabolism. By integrating immune activation with metabolic intervention, nanomedicines not only enhance anti-tumor immunity but also restore metabolic balance, offering a synergistic and potent therapeutic avenue for overcoming treatment resistance and inhibiting tumor progression.