Reprogramming the Breast Cancer Immune Microenvironment Using Nanoparticle-based Therapeutic Platforms

Abstract

Breast cancer is also one of the most common causes of cancerrelated deaths in the world, and this is mainly because of the therapeutic resistance and immune evasion mechanisms in the tumor microenvironment. An immunosuppressive tumor microenvironment, characterized by dysfunctional immune cells and stromal impediments, limits the efficacy of traditional treatments. The strategies of modulating the tumor immune microenvironment using nanoparticles have become promising in improving the outcome of immunotherapies. A structured narrative review was conducted to evaluate the current evidence on nanoparticle-mediated immune modulation in breast cancer. A comprehensive literature search was performed in the PubMed, Scopus, and Web of Science databases to identify relevant studies published between 2015 and 2025. Eligible studies included mechanistic, preclinical (in vitro and in vivo), and clinical investigations examining nanoparticle-based immunotherapeutic approaches and their effects on the breast cancer tumor immune microenvironment. Nanoparticle-based systems, such as lipid-, polymeric-, inorganic-, and biomimetic systems, can be used to deliver therapeutic agents that target key immune components, including tumor-associated macrophages, regulatory T cells, and Cytotoxic T Lymphocytes (CTLs)s. These systems increase antigen presentation and (ICD), which can be used to boost anti-tumor immune responses. Nonetheless, clinical translation remains inadequate due to tumor heterogeneity, transport barriers mediated by the extracellular matrix (ECM), variable delivery efficiency, and safety concerns. Immunomodulatory strategies using nanoparticles enable immune reprogramming and enhance therapeutic targeting in the tumor microenvironment. Although promising preclinical results have been obtained, clinical use is limited due to variable intratumoral distribution, non-uniform immune interactions, and the lack of standardized assessment systems. These issues need to be addressed to enhance translational success. Nanoparticle-mediated immune modulation is a prospective approach to overcome immunosuppression in breast cancer. Future studies must aim to design nanoparticles that maximize tumor uptake, incorporate predictive biomarkers, and optimize clinical utility and therapeutic efficacy.