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  3. Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization

Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization

  • J Nanobiotechnology. 2024 Sep 19;22(1):578. doi: 10.1186/s12951-024-02822-9.
Renpeng Zhou # 1 2 3,  Song Xue # 4 5,  Yuanzhi Cheng # 2,  Yong Chen 1,  Yan Wang 2,  Jing Xing 1 2,  Hao Liu 1 2,  Yucai Xu 1 2,  Yi Lin 1 2,  Zejun Pei 1 2,  Xin Wei 6,  Jie Ding 1 2,  Shufang Li 1,  Ke Wang 1,  Feng Yao 1,  Yingjie Zhao 7 8 9,  Changhai Ding 10 11,  Wei Hu 12 13 14
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
  • 2 The Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, 230032, China.
  • 3 The Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China.
  • 4 Department of Sports Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.
  • 5 Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, 510200, China.
  • 6 Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, People's Republic of China.
  • 7 Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. zyj@ahmu.edu.cn.
  • 8 The Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, 230032, China. zyj@ahmu.edu.cn.
  • 9 The Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China. zyj@ahmu.edu.cn.
  • 10 Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, 510200, China. Changhai.Ding@utas.edu.au.
  • 11 Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. Changhai.Ding@utas.edu.au.
  • 12 Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. huwei@ahmu.edu.cn.
  • 13 The Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, 230032, China. huwei@ahmu.edu.cn.
  • 14 The Key Laboratory of Anti-Inflammatory and Immune Medicine, Anhui Medical University, Ministry of Education, Hefei, 230032, China. huwei@ahmu.edu.cn.
  • # Contributed equally.
PMID: 39300463 DOI: 10.1186/s12951-024-02822-9
Abstract

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints.

Keywords

2-APB; Inflammation; Macrophage polarization; Membrane-encapsulated nanoparticles; Rheumatoid arthritis.

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