Use of Nanoformulation to Target Macrophages for Disease Treatment

Abstract

Macrophages are abundant immune cells, which serve as a primary cell population capable of interacting with foreign substances, including engineered nanomaterials (NMs). In addition to the phagocytic activity, macrophages also play a central role in innate immunity and contribute to the initiation of adaptive immunity. Since macrophages are a natural reservoir for NMs, nanoparticles (or nano-enabled strategies) are commonly utilized to target this cell type and fine tune its polarization status in different disease scenarios. In this review, a high-level description of macrophage biology is first introduced. It is followed by the discussion on the impact of therapeutic NMs on macrophages in solid tumors and how macrophages, in turn, impact the immune system and heterogeneity in the tumor microenvironment. Another major thrust is to discuss the applications of NMs in noncancer diseases with a focus on how NMs can be used to influence macrophages in the process of tissue repair, wound healing, myocardial infarction, and certain autoimmune diseases. In addition to the design of nanocarriers to impact macrophage function, whether the same response outcome can be achieved by intrinsic NM's physicochemical properties, allowing the potential usage of the active pharmaceutical ingredient-free nanomaterials for therapeutic purposes, is also discussed.

Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

“…[49,83,84] Additionally, the composition of the corona, for example, proteins such as albumin, apolipoprotein E (ApoE), and IgG antibodies, will determine the NMs-cell interactions and cellular uptake mechanisms of liver cells once NMs are distributed in the liver. [85][86][87][88][89][90][91][92][93] Among the different liver cells, most studies are focused on the interactions of NMs with KCs, LSECs, HSCs, and hepatocytes due to their important roles in liver physiology and diseases. The unique liver architecture and location of these liver cells profoundly affect their interaction with NMs and cellular uptake, which will eventually determine the cellular responses (Figure 6).…”

“…The encounter of NMs with the biological environments will form a dynamic corona on NMs surfaces, including proteins, lipids, and certain sugar motifs. [85,86] The structure and composition of the corona are determined by the intrinsic physicochemical properties of NMs, the duration of exposure, and the nature of the physiological environment. [87][88][89] It has shown that the biomolecular corona regulated cellular recognition and penetration of NMs, and further influence their intracellular trafficking.…”

On the Cellular Uptake and Exocytosis of Carbon Dots─Significant Cell Type Dependence and Effects of Cell Division

“…Physicochemical properties of NPs, including their shape, size, surface ligand, and so forth, are crucial factors influencing the cellular uptake and exocytosis processes of the NPs. ,− Different cells have different properties and functions, ,− so their responses to different NPs may also be different. For example, cells of different types adopt different endocytic pathways to ingest the same NPs, resulting in different biological effects, for which an example is the higher content of NPs in lysosome destroyed the integrity of the lysosomal membrane. − Different types of cells may also have different proliferation rates, which are correlated with different changes in the cellular content of NPs, with the intracellular NPs almost equally distributed into daughter cells after the cell division. ,, Therefore, the cell type must be a pivotal factor affecting the cellular uptake and exocytosis processes of NPs, as recognized in some reported studies. ,,− Further more systematic investigations on the exocytosis of NPs in cells aimed at an understanding of the cell-type dependence are in demand …”

Smart and Multi-Functional Magnetic Nanoparticles for Cancer Treatment Applications: Clinical Challenges and Future Prospects

“…Phagocytosis of NPs can influence TAM polarization because these particles are recognized as foreign bodies. IONPs demonstrated a potent effect on TAM polarization due to iron transporter-related protein expression [ 311 , 312 , 313 ]. Kodali et al [ 314 ] reported 1029 changes in gene expression of lung macrophages using IONPs while silica NPs with only 67 gene.…”