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Updated: Sep 25, 2025
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Opsonized nanoparticles target and regulate macrophage polarization for osteoarthritis therapy: A trapping strategy
Longfa Kou1, Huirong Huang2, Yingying Tang3
1Wenzhou Municipal Key Laboratory of Pediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Wenzhou key Laboratory of basic science and translational research of radiation oncology, Zhejiang 325027, China.
Abstract:
Osteoarthritis (OA) is a chronic disease caused by joint inflammation. Its occurrence and development depend on a continuous inflammation environment. The activated M1 macrophages play a critical role in the inflammatory response of OA. Regulating the pro-inflammatory M1 to anti-inflammatory M2 macrophages in the OA articular cavity could be a rational strategy for OA treatment. It has been acknowledged that activated macrophages could proactively capture opsonized nanoparticles in the bloodstream and then accumulate into the reticuloendothelial system (RES) organs. Based on this fact, a trapping strategy is proposed, which transforms a normal nanoparticle into an opsonized attractant to target and regulate macrophage polarization. In this study, the opsonized nanoparticle (IgG/Bb@BRPL) had several key features, including an immunoglobulin IgG (the opsonized layer), an anti-inflammatory agent berberine (Bb), and an oxidative stress-responsive bilirubin grafted polylysine biomaterial (BR-PLL) for drug loading (the inner nanocore). In vitro studies confirmed that IgG/Bb@BRPL prefer to be phagocytosed by M1 macrophage, not M0. And the internalized IgG/Bb@BRPL effectively promoted macrophage polarization toward the M2 phenotype and protected nearby chondrocytes. In vivo studies suggested that IgG/Bb@BRPL significantly enhanced therapeutic outcomes by suppressing inflammation and promoting cartilage repair while not prolonging the retention period compared to non-opsonized counterparts. This proof-of-concept study provided a novel opsonization trapping strategy for OA drug delivery and treatment.
Insights
This study introduces a novel nanoparticle strategy to treat osteoarthritis (OA) by targeting M1 macrophages. The opsonized nanoparticles effectively shift macrophage polarization, reducing inflammation and promoting cartilage repair for better OA treatment outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Osteoarthritis (OA) is characterized by chronic joint inflammation driven by M1 macrophages.
- Modulating macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 is a promising therapeutic strategy for OA.
- Activated macrophages can capture opsonized nanoparticles, leading to their accumulation.
Purpose of the Study:
- To develop and evaluate an opsonized nanoparticle strategy for targeting and regulating macrophage polarization in OA.
- To investigate the efficacy of IgG/Bb@BRPL nanoparticles in promoting M2 macrophage polarization and protecting chondrocytes.
- To assess the in vivo therapeutic effects of the opsonized nanoparticles on inflammation and cartilage repair in OA.
Main Methods:
- Designed opsonized nanoparticles (IgG/Bb@BRPL) with an immunoglobulin G layer, berberine drug, and a bilirubin-grafted polylysine core.
- Conducted in vitro studies to assess nanoparticle phagocytosis by M1 macrophages and their effect on macrophage polarization.
- Performed in vivo studies to evaluate the therapeutic outcomes, including inflammation suppression and cartilage repair, compared to non-opsonized nanoparticles.
Main Results:
- In vitro studies showed preferential phagocytosis of IgG/Bb@BRPL by M1 macrophages and successful promotion of M2 polarization.
- Internalized nanoparticles protected adjacent chondrocytes from inflammatory damage.
- In vivo studies demonstrated significant enhancement in therapeutic outcomes, including reduced inflammation and improved cartilage repair, without increased retention time.
Conclusions:
- The opsonization trapping strategy offers a novel approach for targeted drug delivery in OA treatment.
- IgG/Bb@BRPL nanoparticles effectively modulate macrophage polarization, offering a potential therapeutic agent for osteoarthritis.
- This study provides a proof-of-concept for using opsonized nanoparticles to enhance OA treatment efficacy.
