Document Type : Original Article
Authors
1
Cancer Epidemiology Research Center, AJA University of Medical Sciences, Tehran, Iran.
2
Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran. & Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, Iran.
3
School of Business, The Ingenuity Center Nottingham, University of Nottingham, Nottingham, United Kingdom.
4
Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
5
Nanobiotechnology Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
6
Tissue Engineering and Regenerative Medicine Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
7
Department of Food Science and Technology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
8
Trauma Research Center, Aja University of Medical Sciences, Tehran, Iran.
Abstract
Macrophages are pivotal immune cells that exhibit remarkable plasticity, polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to environmental cues. This process, known as macrophage polarization, plays a critical role in the progression and resolution of various diseases, including cancer, inflammatory disorders, and infections. The emergence of nanomedicine has highlighted the significant interplay between nanoparticles and the immune system, positioning macrophages as a key therapeutic target. This review comprehensively examined the immunomodulatory effects of metal-based nanoparticles—specifically copper, titanium, gold, iron, silver, aluminum, and silicon—on macrophage polarization. We detail how intrinsic nanoparticle properties, such as size, shape, surface chemistry, and composition dictate the polarization outcome by modulating specific molecular pathways, including NF-κB, STAT, IRF, and MAPK signaling. For instance, while iron oxide and certain titanium nanoparticles (TNPs) typically promote M1 polarization, gold and silicon nanoparticles are often shown to induce an M2 phenotype. The effects of other metals, like copper and silver, are highly concentration-dependent or can be tailored through surface functionalization. This analysis underscores the potential of engineered metal nanoparticles to precisely direct macrophage polarization for therapeutic benefit, such as repolarizing tumor-associated macrophages for cancer immunotherapy or promoting M2-mediated tissue regeneration in wound healing. Understanding these intricate interactions is crucial for advancing the application of nanomedicine in immunotherapy and for assessing the safety profile of nanomaterials.
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