Nanoparticles Targeting Macrophages as Potential Clinical Therapeutic Agents Against Cancer and Inflammation

Abstract

With the development of nanotechnology, significant progress has been made in the design, and manufacture of nanoparticles (NPs) for use in clinical treatments. Recent increases in our understanding of the central role of macrophages in the context of inflammation and cancer have reinvigorated interest in macrophages as drug targets. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in cancer and inflammation processes. Thus, NPs tailored to accurately target macrophages have the potential to transform disease treatment. Herein, we first present a brief background information of NPs as drug carriers, including but not limited to the types of nanomaterials, their biological properties and their advantages in clinical application. Then, macrophage effector mechanisms and recent NPs-based strategies aimed at targeting macrophages by eliminating or re-educating macrophages in inflammation and cancer are summarized. Additionally, the development of nanocarriers targeting macrophages for disease diagnosis is also discussed. Finally, the significance of macrophage-targeting nanomedicine is highlighted, with the goal of facilitating future clinical translation.

Keywords: drug delivery; inflammation; macrophages; nanoparticles; tumor.

Figure 1

Summary of the fundamental features of NPs as carriers for drug delivery.

Figure 2

The origin and polarization of macrophages. Tissue macrophages are derived from hematopoietic stem cell (HSC) progenitor cells and exist in blood as monocytes under homeostatic conditions. Monocytes migrate into tissue and differentiate into different macrophages induced by physiologic stimuli, which are associated with a response to inflammatory and cancer conditions.

Figure 3

Macrophage subtypes play different roles in inflammation and cancer. In response to various stimuli, such as inflammation, M1 macrophages promote the progression of inflammation, while M2 macrophages mainly play an anti-inflammatory role. Nevertheless, M1 macrophages are mainly involved in antitumor immunity, while M2 macrophages promote tumor growth and invasion in the tumor microenvironment (TME). The dynamic balance between M1 and M2 macrophages jointly determines the evolution of inflammation and tumors.

Figure 4

Strategies for nanoparticles packaged with therapeutic agents to target M1 macrophages in inflammation leading to M1 macrophage depletion and re-education.

Figure 5

Schemes for nanoparticles loaded with specific agents to target TAM signaling pathways. Nanoparticles target TAMs in the TME via two mechanisms, TAM depletion and TAM reprogramming. The former includes the inhibition of recruitment by blocking the CCL2-CCR2 signaling pathway and survival interference via inhibiting the CSF1-CSF1R signaling pathway. The latter mainly involves cellular re-education to change TAMs into M1 macrophages.