Current Insights into Interaction of Metallic Nanoparticles with the Tumor Microenvironment

Cancer remains one of the most significant health challenges facing humanity today. Extensive oncological research has demonstrated that cancer progression is not solely driven by malignant cells but also by the tumor microenvironment (TME), which plays a crucial role in tumor development, immune evasion and metastasis. As a result, the TME has emerged as a promising therapeutic target. Nanotechnology has revolutionized cancer diagnosis and treatment, with metallic nanoparticles (mNPs) being extensively studied. However, their effects on the TME remain poorly understood. While some molecular pathways through which mNPs influence the TME have been identified, these findings likely represent only a small fraction of the underlying mechanisms, as analyzed in this review. Furthermore, a major challenge in studying these interactions is the lack of physiologically relevant models, as currently available cell culture and in vivo systems often fail to accurately replicate the complex and dynamic interactions of the TME. These limitations underscore the urgent need for more comprehensive research to establish the TME as a viable therapeutic target for treatment strategies involving NPs. Specifically, a deeper understanding of how mNPs interact with the TME at multiple levels, including immune modulations, stromal remodeling and metabolic reprogramming, is essential toward optimizing the therapeutic potential of mNPs in cancer care.