Targeting breast tumor extracellular matrix and stroma utilizing nanoparticles

Abstract

Breast cancer is a complicated malignancy and is known as the most common cancer in women. Considerable experiments have been devoted to explore the basic impacts of the tumor stroma, particularly the extracellular matrix (ECM) and stromal components, on tumor growth and resistance to treatment. ECM is made up of an intricate system of proteins, glycosaminoglycans, and proteoglycans, and maintains structural support and controls key signaling pathways involved in breast tumors. ECM can block different drugs such as chemotherapy and immunotherapy drugs from entering the tumor stroma. Furthermore, the stromal elements, such as cancer-associated fibroblasts (CAFs), immune cells, and blood vessels, have crucial impacts on tumor development and therapeutic resistance. Recently, promising outcomes have been achieved in using nanotechnology for delivering drugs to tumor stroma and crossing ECM in breast malignancies. Nanoparticles have various benefits for targeting the breast tumor stroma, such as improved permeability and retention, extended circulation time, and the ability to actively target the area. This review covers the latest developments in nanoparticle therapies that focus on breast tumor ECM and stroma. We will explore different approaches using nanoparticles to target the delivery of anticancer drugs like chemotherapy, small molecule drugs, various antitumor products, and other specific synthetic therapeutic agents to the breast tumor stroma. Furthermore, we will investigate the utilization of nanoparticles in altering the stromal elements, such as reprogramming CAFs and immune cells, and also remodeling ECM.

Keywords: Breast cancer; Cancer-associated fibroblasts (CAFs); Extracellular matrix (ECM); Nanoparticles; Tumor stroma.