Nano-therapeutic targeting of the tumor microenvironment in metastatic breast cancer: Current state and future prospects

The tumour-microenvironment (TME) is a complex network of cells and molecules that has a major impact on the development, dissemination, and progression of cancer metastasis. It is made up of stromal cells, tumour cells, cancer-associated blood and lymphatic vessels, pericytes, cancer-associated fibroblasts, cancer-stem cells, and extracellular matrix (ECM). Metastatic breast cancer is one of the most difficult to treat forms of the disease. This calls for a comprehensive comprehension of the metastatic TME and the development of novel nano-drug delivery systems that leverage specific cellular components. Nanoparticles (NPs) that respond to external stimuli provide improved control over where and when cells are targeted. Nano-therapies need to be safe, effective and scalable in manufacturing for translation to clinics. Emerging nano-strategies, in contrast to traditional medicines that promote systemic ablation, selectively control the diverse TME cell populations by, for example, focusing on pericytes and endothelial cells to normalize vascular function. We also describe the gaps in the present nanotherapeutics approaches and highlight innovative views on the design of pre-clinical and clinical trials to alter breast cancer's ability to spread.