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Purpose <p>Delivering immunogloblin G (IgG) to the articular cartilage is a challenge and presents an obstacle in developing therapeutic antibodies for articular diseases. In this study, we focused on binding to the aggrecan—a key component of the cartilage matrix as a proteoglycan—and molecular downsizing to enhance the penetration and retention of antibodies in the articular cartilage.</p> Methods <p>The control IgG (143&#xa0;kDa), anti-aggrecan IgG (141&#xa0;kDa), F(ab’)2 (93.0&#xa0;kDa), and Fab (44.9&#xa0;kDa) were intra-articularly injected into a rabbit joint, and the concentrations of each molecule in synovial fluid, articular cartilage, and plasma were monitored.</p> Results <p>Each molecule exhibited a similar elimination profile in synovial fluid. However, compared to the control IgG, anti-aggrecan IgG showed increased exposure in cartilage. Moreover, anti-aggrecan F(ab’)2 exhibited even higher concentrations in cartilage, while the anti-aggrecan Fab demonstrated the highest and most long-lasting concentration profile in cartilage. Fluorescence imaging of the <i>ex vivo</i> cartilage penetration further supported the superior transport of the anti-aggrecan Fab and F(ab’)2 compared to the control IgG and the anti-aggrecan IgG.</p> Conclusions <p>Our study demonstrates that binding to the cartilage matrix, in addition to molecular size, is important, and that their combination has a synergistic effect on the antibody exposure in the articular cartilage.</p>

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Enhanced Penetration and Retention of an Antibody in the Articular Cartilage Through Aggrecan Binding and Molecular Downsizing

  • 期刊论文

  • 发表日期：

    2025年3月17日

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  • Yuki Noguchi,
  • Maiko Hoshino,
  • Masaru Muraoka,
  • Garvita Gupta,
  • Yang Sun,
  • Naoka Hironiwa,
  • Wenjie Tu,
  • Eri Joyashiki,
  • Kenta Haraya,
  • Taichi Kuramochi,
  • Tomoyuki Igawa

摘要

Purpose

Delivering immunogloblin G (IgG) to the articular cartilage is a challenge and presents an obstacle in developing therapeutic antibodies for articular diseases. In this study, we focused on binding to the aggrecan—a key component of the cartilage matrix as a proteoglycan—and molecular downsizing to enhance the penetration and retention of antibodies in the articular cartilage.

Methods

The control IgG (143 kDa), anti-aggrecan IgG (141 kDa), F(ab’)2 (93.0 kDa), and Fab (44.9 kDa) were intra-articularly injected into a rabbit joint, and the concentrations of each molecule in synovial fluid, articular cartilage, and plasma were monitored.

Results

Each molecule exhibited a similar elimination profile in synovial fluid. However, compared to the control IgG, anti-aggrecan IgG showed increased exposure in cartilage. Moreover, anti-aggrecan F(ab’)2 exhibited even higher concentrations in cartilage, while the anti-aggrecan Fab demonstrated the highest and most long-lasting concentration profile in cartilage. Fluorescence imaging of the ex vivo cartilage penetration further supported the superior transport of the anti-aggrecan Fab and F(ab’)2 compared to the control IgG and the anti-aggrecan IgG.

Conclusions

Our study demonstrates that binding to the cartilage matrix, in addition to molecular size, is important, and that their combination has a synergistic effect on the antibody exposure in the articular cartilage.