Skip to main content
ISPRM 2026 Main banner
Final Program


Final Congress Guide

Biomedical Sciences

100 Section - ROS-responsive PROTAC nanoparticles as a drug delivery system for targeting COX2 inhibition in the attenuation of osteoarthritis

Wednesday, May 20, 2026
6:00 PM - 7:30 PM PT

    Presenting Author/Autor expositor(s)

  • JH

    Jing Hu, n/a

    Research Associate
    Rehabilitation Key Laboratory of Sichuan Province
    OMAHA, Nebraska, United States

    • Corresponding Author/Autor a quien dirigir la corr(s)

  • CH

    Chengqi He, MD

    professor
    Sichuan University West China Hospital Rehabilitation Medical Center
    Chengdu, Sichuan, China (People's Republic)

Objectives : Knee osteoarthritis (KOA), a degenerative joint disease, involves chronic inflammation and cartilage destruction. COX-2, overexpressed in inflammation, exacerbates oxidative stress, causing pain and swelling. NSAIDs like indomethacin inhibit COX-2 but have long-term side effects. This study introduces a novel strategy using PROTACs and ROS-responsive nanotechnology to target COX-2, reduce inflammation, and minimize adverse effects, offering a safer, more effective KOA treatment.

Design:

This study developed a COX-2-targeting PROTAC molecule (Ind-Pam) using indomethacin and pomalidomide, encapsulated within a ROS-responsive polymer (PBAP-NPs) to form Ind-Pam-PBAP nanoparticles. The system's physicochemical properties, including size, stability, and ROS-triggered drug release, were characterized. In vitro studies assessed cytotoxicity, COX-2 degradation, and anti-inflammatory effects on chondrocytes and macrophages. In vivo, C57BL/6 mice with DMM-induced KOA were treated with IPP-PBAP-NPs, evaluating inflammation, cartilage repair, and pain relief through histopathology, immunohistochemistry, imaging, and behavioral assays.

Results:

The nanostructure and characterization of the nanoparticles were confirmed, with size and TEM analyses demonstrating ROS-triggered structural disruption and drug release. In vitro, cellular uptake occurred via endocytosis. The nanoparticles inhibited M2 macrophage polarization and suppressed COX-2 expression in chondrocytes and macrophages, as confirmed by PCR and WB. In inflammatory chondrocyte models, the nanoparticles upregulated SOX9 and collagen II while downregulating MMP13. In vivo, immunohistochemistry revealed reduced COX-2 expression, and DMM model mice exhibited improved gait symmetry and cartilage integrity following intravenous administration, demonstrating the therapeutic potential of this ROS-responsive nanodelivery system for KOA treatment.

Conclusion:

The ROS-responsive Ind-Pam-PBAP system effectively targets and degrades COX-2, reducing inflammation and promoting cartilage repair in KOA. This innovative approach demonstrates significant therapeutic potential, offering a precise, safe, and efficient strategy for KOA treatment by enhancing drug delivery and minimizing systemic side effects.