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Research Article

MCP-1 and IL-4 encapsulated hydrogel particles with macrophages enrichment and polarization capabilities for systemic lupus erythematosus treatment

Shengjie Zhu1Danqing Huang1Qichen Luan1Yang Li1Jingjing Gan1()Yuanjin Zhao1,2()Lingyun Sun1()
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210096, China
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
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We developed a hyaluronic acid methacrylate (HAMA) hydrogel delivery system containing monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) to alleviate renal lesions in systemic lupus erythematosus (SLE) by recruiting and polarizing macrophages to exert immunomodulatory functions.

Abstract

Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.

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Nano Research
Pages 8316-8324
Cite this article:
Zhu S, Huang D, Luan Q, et al. MCP-1 and IL-4 encapsulated hydrogel particles with macrophages enrichment and polarization capabilities for systemic lupus erythematosus treatment. Nano Research, 2024, 17(9): 8316-8324. https://doi.org/10.1007/s12274-024-6794-z
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