Nanomedicine-based cancer immunotherapies developed by reprogramming tumor-associated macrophages

Tumor microenvironment is a complex ecosystem composed of tumor extracellular matrix, fibroblasts, blood vessels, and immune cells, promoting tumor development by secreting various growth factors, hydrolase, and inflammatory factors. Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the TME, and they have a "double-edged sword" effect on tumor growth, invasion, metastasis, angiogenesis, and immunosuppression. Under the regulation of different cytokines in the TME, the bidirectional TAMs can switch their phenotypes between tumoricidal M1-like and pro-tumorigenic M2-like macrophages. TAM polarization suggests that scientists can use this property to design drugs targeting this regulation as a promising immunotherapy strategy to enhance tumor therapy efficiency. In this review, we summarize a brief introduction of TAMs and their implications for tumorigenesis. Next, we review recent advances in designing various functionalized nanomedicines and their applications in nanomedicine-based cancer therapies that target TAMs by killing them, inhibiting macrophage recruitment, and repolarizing them from pro-tumorigenic M2-like to tumoricidal M1-like macrophages. Simultaneously, the regulation of nanomedicines on the signaling pathways accounting for these effects is also summarized. This review will not only provide background scientific information for the understanding of TAMs and their roles in cancer treatment but also help scientists design nanomedicines based on tumor TAMs, which can help achieve better clinical treatment outcomes for tumors.