Modulating Repolarization of Tumor-Associated Macrophages with Targeted Therapeutic Nanoparticles as a Potential Strategy for Cancer Therapy.

Abstract

There are always some components in the tumor microenvironment (TME), such as tumor-associated macrophages (TAMs), that help tumor cells escape the body's immune surveillance. Therefore, this situation can lead to tumor growth, progression, and metastasis, resulting in low response rates for cancer therapy. Macrophages play an important role with strong plasticity and functional diversity. Facing different microenvironmental stimulations, macrophages undergo a dynamic change in phenotype and function into two major macrophage subpopulations, namely classical activation/inflammation (M1) and alternative activation/regeneration (M2) type. Through various signaling pathways, macrophages polarize into complex groups, which can perform different immune functions. In this review, we emphasize the use of nanopreparations for macrophage related immunotherapy based on the pathological knowledge of TAMs phenotype. These macrophages targeted nanoparticles re-edit and re-educate macrophages by attenuating M2 macrophages and reducing aggregation to the TME, thereby relieving or alleviating immunosuppression. Among them, we describe in detail the cellular mechanisms and regulators of several major signaling pathways involved in the plasticity and polarization functions of macrophages. The advantages and challenges of those nanotherapeutics for these pathways have been elucidated, providing the basis and insights for the diagnosis and treatment strategies of various diseases centered on macrophages.