Research progress on the effect of iron oxide nanoparticles in macrophage polarization_Journal of Biomedical Engineering

Authors：

ZHANG Haojie , ZHANG Xinyu , FENG Yachan , DU Chao ,  WANG Yingze , GUO Xueling

College of Food Science and Biology, Hebei University of Science and Technology, Shijiazhuang 050018, P.R. China;

Corresponding author：

Keywords：

Macrophages; Polarization effect; Iron oxide nanoparticles; Reprogramming

DOI：

10.7507/1001-5515.202209027

Video：

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Macrophages are important immune effector cells with significant plasticity and heterogeneity in the body immune system, and play an important role in normal physiological conditions and in the process of inflammation. It has been found that macrophage polarization involves a variety of cytokines and is a key link in immune regulation. Targeting macrophages by nanoparticles has a certain impact on the occurrence and development of a variety of diseases. Due to its characteristics, iron oxide nanoparticles have been used as the medium and carrier for cancer diagnosis and treatment, making full use of the special microenvironment of tumors to actively or passively aggregate drugs in tumor tissues, which has a good application prospect. However, the specific regulatory mechanism of reprogramming macrophages using iron oxide nanoparticles remains to be further explored. In this paper, the classification, polarization effect and metabolic mechanism of macrophages were firstly described. Secondly, the application of iron oxide nanoparticles and the induction of macrophage reprogramming were reviewed. Finally, the research prospect and difficulties and challenges of iron oxide nanoparticles were discussed to provide basic data and theoretical support for further research on the mechanism of the polarization effect of nanoparticles on macrophages.

Citation： ZHANG Haojie, ZHANG Xinyu, FENG Yachan, DU Chao, WANG Yingze, GUO Xueling. Research progress on the effect of iron oxide nanoparticles in macrophage polarization. Journal of Biomedical Engineering, 2023, 40(2): 384-391. doi: 10.7507/1001-5515.202209027 Copy

1.	Salah A, Li Y, Wang H, et al. Macrophages as a double-edged weapon: The use of macrophages in cancer immunotherapy and understanding the cross-talk between macrophages and cancer. DNA Cell Biol, 2021, 40: 429-440.
2.	de Groot A E, Pienta K J. Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages. Oncotarget, 2018, 9(29): 20908-20927.
3.	金萧萧, 王彩莲. 氧化铁纳米颗粒在恶性肿瘤诊疗中的应用及进展. 现代肿瘤医学, 2017, 25(17): 2852-2855.
4.	Yuan H S, Wilks M Q, El Fakhri G, et al. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials. PLoS One, 2017, 12(2): e0172722.
5.	Kaittanis C, Bolaender A, Yoo B, et al. Targetable clinical nanoparticles for precision cancer therapy based on disease-specific molecular inflection points. Nano Lett, 2017, 17: 7160-7168.
6.	李康, 郭强, 王翠妮, 等. M1和M2型巨噬细胞表型的比较分析. 现代免疫学, 2008, 28(3): 177-183.
7.	Funes S C, Rios M, Escobar-Vera J, et al. Implications of macrophage polarization in autoimmunity. Immunol, 2018, 154(2): 186-195.
8.	Galvan-Pena S, O’Neill L A. Metabolic reprograming in macrophage polarization. Front in Immunol, 2014, 5: 420.
9.	Bowdish D. Macrophage activation and polarization. Encycl Immunobiol, 2016, 1: 289-292.
10.	赵清杰, 朱琳楠, 丁文军, 等. 巨噬细胞极化与细胞代谢的相互调控. 细胞与分子免疫学杂志, 2015, 31(3): 408-411.
11.	柳笑彦, 刘力. 代谢及炎症反应相关的巨噬细胞极化调控的研究进展. 转化医学电子杂志, 2018, 5(10): 92-96.
12.	Orliaguet L, Dalmas E, Drareni K, et al. Mechanisms of macrophage polarization in insulin signaling and sensitivity. Front in Endocrinol, 2020, 11: 62.
13.	Irey E A, Lassiter C M, Brady N J, et al. JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors. Proc Natl Acad Sci, 2019, 116: 12442-12451.
14.	Xin P, Xu X, Deng C, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol, 2020, 80: 1-11.
15.	Zhang T, Ma C, Zhang Z, et al. NF-κB signaling in inflammation and cancer. MedComm (2020), 2021, 2(4): 618-653.
16.	Savitsky D, Tamura T, Yanai H, et al. Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother, 2010, 59(4): 489-510.
17.	Bouhlel M A, Derudas B, Rigamonti E, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory propertie. Cell Metab, 2007, 6(2): 137-143.
18.	Shu Y, Qin M, Song Y, et al. M2 polarization of tumor-associated macrophages is dependent on integrin β3 via peroxisome proliferator-activated receptor-γ up-regulation in breast cancer. Immunology, 2020, 160(4): 345-356.
19.	Li C, Xu M M, Wang K, et al. Macrophage polarization and meta-inflammation. Transl Res, 2018, 191: 29-44.
20.	Saha B, Bala S, Hosseini N, et al. Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease. J Leukoc Biol, 2015, 97(5): 963-973.
21.	Mohajerani A, Burnett L, Smith J V, et al. Nanoparticles in construction materials and other applications, and implications of nanoparticle use. Materials (Basel), 2019, 12(19): 3052.
22.	Chaturvedi V, Singh A, Singh V, et al. Cancer nanotechnology: A new revolution for cancer diagnosis and therapy. Current Drug Metabol, 2019, 20(6): 416-429.
23.	朴美玉, 赵经文. 磁性氧化铁纳米粒子在生物医学应用中的研究进展. 淮海医药, 2020, 38(4): 436-439.
24.	Colombo M, Carregal-Romero S, Casula M F, et al. Biological applications of magnetic nanoparticles. Chem Soc Rev, 2012, 41(11): 4306-4334.
25.	Kiessling F, Mertens M E, Grimm J, et al. Nanoparticles for imaging: Top or Flop? Radiol, 2014, 273: 10-28.
26.	Merinopoulos I, Gunawardena T, Stirrat C, et al. Diagnostic applications of ultrasmall superparamagnetic particles of iron oxide for imaging myocardial and vascular inflammation. JACC Card Imag, 2021, 14(6): 1249-1264.
27.	Dulińska-Litewka J, Łazarczyk A, Hałubiec P, et al. Superparamagnetic iron oxide nanoparticles-current and prospective medical applications. Materials (Basel), 2019, 12(4): 617.
28.	Kono Y, Gogatsubo S, Ohba T, et al. Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field. Drug Deliv, 2019, 26(1): 935-943.
29.	Kang M K, Kim T J, Kim Y J, et al. Targeted delivery of iron oxide nanoparticle-loaded human embryonic stem cell-derived spherical neural masses for treating intracerebral hemorrhage. Int J Mol Sci, 2020, 21(10): 3658.
30.	Mertz D, Sandre O, Begin-Colin S. Drug releasing nanoplatforms activated by alternating magnetic fields. Biochim Biophys Acta, 2017, 1861: 1617-1641.
31.	Thiesen B, Jordan A. Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperthermia, 2008, 24: 467-474.
32.	Kumar C S S R, Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev, 2011, 63: 789-808.
33.	Golovin Y I, Gribanovsky S L, Golovin D Y, et al. Towards nanomedicines of the future: Remote magneto-mechanical actuation of nanomedicines by alternating magnetic fields. J Control Release, 2015, 219: 43-60.
34.	Laskar A, Eilertsen J, Li W, et al. SPION primes THP1 derived M2 macrophages towards M1-like macrophages. Biochem Biophys Res Commun, 2013, 441(4): 737-742.
35.	Liao Z X, Ou D L, Hsieh M J, et al. Synergistic effect of repolarization of M2 to M1 macrophages induced by iron oxide nanoparticles combined with lactate oxidase. Int J Mol Sci, 2021, 22(24): 13346.
36.	付倩梅, 唐华明, 张鹏, 等. 偶联 CD206 抗体载 Fe₃O₄ 的 PLGA 纳米微球促进巨噬细胞 M1 型极化. 南方医科大学学报, 2020, 40(2): 246-254.
37.	Li C X, Zhang Y, Dong X, et al. Artificially reprogrammed macrophages as tumor-tropic immunosuppression-resistant biologics to realize therapeutics production and immune activation. Adv Mater, 2019, 31(15): e1807211.
38.	Zhang W, Cao S, Liang S, et al. Differently charged super-paramagnetic iron oxide nanoparticles preferentially induced M1-like phenotype of macrophages. Front Bioeng Biot, 2020, 8: 537.
39.	齐奥, 付宜鸣, 倪少滨. 氧化铁纳米颗粒通过诱导巨噬细胞释放活性氧抑制膀胱癌的研究. 中国免疫学杂志, 2019, 35(12): 1473-1475, 1481.
40.	DeNardo D G, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol, 2019, 19(6): 369-382.
41.	Sukhbaatar N, Weichhart T. Iron regulation: macrophages in control. Pharmaceuticals, 2018, 11(4): 137.
42.	Nascimento C S, Alves É A R, Melo C P, et al. Immunotherapy for cancer: effects of iron oxide nanoparticles on polarization of tumor-associated macrophages. Nanomed (Lond), 2021, 16: 2633-2650.
43.	Guo W, Wu X, Wei W, et al. Mesoporous hollow Fe₃O₄ nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field. J Mater Chem B, 2022, 10(29): 5633-5643.
44.	Nwasike C, Yoo E, Purr E, et al. Activatable superparamagnetic iron oxide nanoparticles scavenge reactive oxygen species in macrophages and endothelial cells. RSC Adv, 2020, 10(68): 41305-41314.
45.	Lei H, Pan Y, Wu R, et al. Innate immune regulation under magnetic fields with possible mechanisms and therapeutic applications. Front Immunol, 2020, 11: 1-10.
46.	Lee J H, Ju J E, Kim B I, et al. Rod-shaped iron oxide nanoparticles are more toxic than sphere-shaped nanoparticles to murine macrophage cells. Environ Toxicol Chem, 2014, 33(12): 2759-2766.
47.	Chen S, Chen S, Zeng Y, et al. Size-dependent superparamagnetic iron oxide nanoparticles dictate interleukin-1β release from mouse bone marrow-derived macrophages. J Appl Toxicol, 2018, 38(7): 978-986.
48.	Feng Q, Liu Y, Huang J, et al. Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci Rep, 2018, 8(1): 1-13.

1. Salah A, Li Y, Wang H, et al. Macrophages as a double-edged weapon: The use of macrophages in cancer immunotherapy and understanding the cross-talk between macrophages and cancer. DNA Cell Biol, 2021, 40: 429-440.
2. de Groot A E, Pienta K J. Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages. Oncotarget, 2018, 9(29): 20908-20927.
3. 金萧萧, 王彩莲. 氧化铁纳米颗粒在恶性肿瘤诊疗中的应用及进展. 现代肿瘤医学, 2017, 25(17): 2852-2855.
4. Yuan H S, Wilks M Q, El Fakhri G, et al. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials. PLoS One, 2017, 12(2): e0172722.
5. Kaittanis C, Bolaender A, Yoo B, et al. Targetable clinical nanoparticles for precision cancer therapy based on disease-specific molecular inflection points. Nano Lett, 2017, 17: 7160-7168.
6. 李康, 郭强, 王翠妮, 等. M1和M2型巨噬细胞表型的比较分析. 现代免疫学, 2008, 28(3): 177-183.
7. Funes S C, Rios M, Escobar-Vera J, et al. Implications of macrophage polarization in autoimmunity. Immunol, 2018, 154(2): 186-195.
8. Galvan-Pena S, O’Neill L A. Metabolic reprograming in macrophage polarization. Front in Immunol, 2014, 5: 420.
9. Bowdish D. Macrophage activation and polarization. Encycl Immunobiol, 2016, 1: 289-292.
10. 赵清杰, 朱琳楠, 丁文军, 等. 巨噬细胞极化与细胞代谢的相互调控. 细胞与分子免疫学杂志, 2015, 31(3): 408-411.
11. 柳笑彦, 刘力. 代谢及炎症反应相关的巨噬细胞极化调控的研究进展. 转化医学电子杂志, 2018, 5(10): 92-96.
12. Orliaguet L, Dalmas E, Drareni K, et al. Mechanisms of macrophage polarization in insulin signaling and sensitivity. Front in Endocrinol, 2020, 11: 62.
13. Irey E A, Lassiter C M, Brady N J, et al. JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors. Proc Natl Acad Sci, 2019, 116: 12442-12451.
14. Xin P, Xu X, Deng C, et al. The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol, 2020, 80: 1-11.
15. Zhang T, Ma C, Zhang Z, et al. NF-κB signaling in inflammation and cancer. MedComm (2020), 2021, 2(4): 618-653.
16. Savitsky D, Tamura T, Yanai H, et al. Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother, 2010, 59(4): 489-510.
17. Bouhlel M A, Derudas B, Rigamonti E, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory propertie. Cell Metab, 2007, 6(2): 137-143.
18. Shu Y, Qin M, Song Y, et al. M2 polarization of tumor-associated macrophages is dependent on integrin β3 via peroxisome proliferator-activated receptor-γ up-regulation in breast cancer. Immunology, 2020, 160(4): 345-356.
19. Li C, Xu M M, Wang K, et al. Macrophage polarization and meta-inflammation. Transl Res, 2018, 191: 29-44.
20. Saha B, Bala S, Hosseini N, et al. Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease. J Leukoc Biol, 2015, 97(5): 963-973.
21. Mohajerani A, Burnett L, Smith J V, et al. Nanoparticles in construction materials and other applications, and implications of nanoparticle use. Materials (Basel), 2019, 12(19): 3052.
22. Chaturvedi V, Singh A, Singh V, et al. Cancer nanotechnology: A new revolution for cancer diagnosis and therapy. Current Drug Metabol, 2019, 20(6): 416-429.
23. 朴美玉, 赵经文. 磁性氧化铁纳米粒子在生物医学应用中的研究进展. 淮海医药, 2020, 38(4): 436-439.
24. Colombo M, Carregal-Romero S, Casula M F, et al. Biological applications of magnetic nanoparticles. Chem Soc Rev, 2012, 41(11): 4306-4334.
25. Kiessling F, Mertens M E, Grimm J, et al. Nanoparticles for imaging: Top or Flop? Radiol, 2014, 273: 10-28.
26. Merinopoulos I, Gunawardena T, Stirrat C, et al. Diagnostic applications of ultrasmall superparamagnetic particles of iron oxide for imaging myocardial and vascular inflammation. JACC Card Imag, 2021, 14(6): 1249-1264.
27. Dulińska-Litewka J, Łazarczyk A, Hałubiec P, et al. Superparamagnetic iron oxide nanoparticles-current and prospective medical applications. Materials (Basel), 2019, 12(4): 617.
28. Kono Y, Gogatsubo S, Ohba T, et al. Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field. Drug Deliv, 2019, 26(1): 935-943.
29. Kang M K, Kim T J, Kim Y J, et al. Targeted delivery of iron oxide nanoparticle-loaded human embryonic stem cell-derived spherical neural masses for treating intracerebral hemorrhage. Int J Mol Sci, 2020, 21(10): 3658.
30. Mertz D, Sandre O, Begin-Colin S. Drug releasing nanoplatforms activated by alternating magnetic fields. Biochim Biophys Acta, 2017, 1861: 1617-1641.
31. Thiesen B, Jordan A. Clinical applications of magnetic nanoparticles for hyperthermia. Int J Hyperthermia, 2008, 24: 467-474.
32. Kumar C S S R, Mohammad F. Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. Adv Drug Deliv Rev, 2011, 63: 789-808.
33. Golovin Y I, Gribanovsky S L, Golovin D Y, et al. Towards nanomedicines of the future: Remote magneto-mechanical actuation of nanomedicines by alternating magnetic fields. J Control Release, 2015, 219: 43-60.
34. Laskar A, Eilertsen J, Li W, et al. SPION primes THP1 derived M2 macrophages towards M1-like macrophages. Biochem Biophys Res Commun, 2013, 441(4): 737-742.
35. Liao Z X, Ou D L, Hsieh M J, et al. Synergistic effect of repolarization of M2 to M1 macrophages induced by iron oxide nanoparticles combined with lactate oxidase. Int J Mol Sci, 2021, 22(24): 13346.
36. 付倩梅, 唐华明, 张鹏, 等. 偶联 CD206 抗体载 Fe₃O₄ 的 PLGA 纳米微球促进巨噬细胞 M1 型极化. 南方医科大学学报, 2020, 40(2): 246-254.
37. Li C X, Zhang Y, Dong X, et al. Artificially reprogrammed macrophages as tumor-tropic immunosuppression-resistant biologics to realize therapeutics production and immune activation. Adv Mater, 2019, 31(15): e1807211.
38. Zhang W, Cao S, Liang S, et al. Differently charged super-paramagnetic iron oxide nanoparticles preferentially induced M1-like phenotype of macrophages. Front Bioeng Biot, 2020, 8: 537.
39. 齐奥, 付宜鸣, 倪少滨. 氧化铁纳米颗粒通过诱导巨噬细胞释放活性氧抑制膀胱癌的研究. 中国免疫学杂志, 2019, 35(12): 1473-1475, 1481.
40. DeNardo D G, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol, 2019, 19(6): 369-382.
41. Sukhbaatar N, Weichhart T. Iron regulation: macrophages in control. Pharmaceuticals, 2018, 11(4): 137.
42. Nascimento C S, Alves É A R, Melo C P, et al. Immunotherapy for cancer: effects of iron oxide nanoparticles on polarization of tumor-associated macrophages. Nanomed (Lond), 2021, 16: 2633-2650.
43. Guo W, Wu X, Wei W, et al. Mesoporous hollow Fe₃O₄ nanoparticles regulate the behavior of neuro-associated cells through induction of macrophage polarization in an alternating magnetic field. J Mater Chem B, 2022, 10(29): 5633-5643.
44. Nwasike C, Yoo E, Purr E, et al. Activatable superparamagnetic iron oxide nanoparticles scavenge reactive oxygen species in macrophages and endothelial cells. RSC Adv, 2020, 10(68): 41305-41314.
45. Lei H, Pan Y, Wu R, et al. Innate immune regulation under magnetic fields with possible mechanisms and therapeutic applications. Front Immunol, 2020, 11: 1-10.
46. Lee J H, Ju J E, Kim B I, et al. Rod-shaped iron oxide nanoparticles are more toxic than sphere-shaped nanoparticles to murine macrophage cells. Environ Toxicol Chem, 2014, 33(12): 2759-2766.
47. Chen S, Chen S, Zeng Y, et al. Size-dependent superparamagnetic iron oxide nanoparticles dictate interleukin-1β release from mouse bone marrow-derived macrophages. J Appl Toxicol, 2018, 38(7): 978-986.
48. Feng Q, Liu Y, Huang J, et al. Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci Rep, 2018, 8(1): 1-13.

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