Publications

The tumor microenvironment (TME) plays a pivotal role in cancer initiation, progression, metastasis, and therapeutic resistance. It comprises a dynamic and complex network of tumor cells, stromal cells, immune cells, extracellular matrix (ECM), cytokines, and blood vessels that collectively support tumor growth. Conventional cancer therapies often fail to address the multifaceted nature of the TME, resulting in limited efficacy and relapse. Nanotechnology offers an innovative platform to precisely modulate the TME by reprogramming its components and restoring antitumor immunity. This review provides a comprehensive analysis of the current advances in nanotechnology-based strategies for TME modulation, including normalization of tumor vasculature, remodeling of the ECM, reprogramming of tumor-associated macrophages (TAMs), targeting cancer-associated fibroblasts (CAFs), alleviating hypoxia, and modulating immunosuppressive pathways. We also discuss the design considerations of nanocarriers, such as size, surface charge, and targeting ligands, which enhance their accumulation and retention in the tumor site. Furthermore, we highlight the integration of nanotechnology with emerging therapies such as immune checkpoint inhibitors, CAR-T cells, and tumor vaccines to achieve synergistic effects. Despite promising preclinical results, challenges remain in translating these approaches to the clinic due to heterogeneity of the TME, nanotoxicity concerns, and regulatory hurdles. Future perspectives call for the development of multifunctional, stimuli-responsive, and personalized nanomedicine to achieve efficient TME reprogramming and improved cancer outcomes.