2. Academic Validation
  3. Zn2+-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-κB signaling and activating autophagy

Zn2+-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-κB signaling and activating autophagy

  • Biomaterials. 2025 Aug:319:123210. doi: 10.1016/j.biomaterials.2025.123210.
Haoqiang He 1,  Chanting Huang 1,  Hongjun Huang 1,  Nihan Lan 1,  Siyi Liu 2,  Yan Luo 1,  Li Zheng 3,  Gang Liu 4,  Zainen Qin 5,  Jinmin Zhao 6
Affiliations

Affiliations

  • 1 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
  • 2 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
  • 3 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China. Electronic address: zhengli@gxmu.edu.cn.
  • 4 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China. Electronic address: gangliu.cmitm@xmu.edu.cn.
  • 5 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China. Electronic address: qinzainen@sr.gxmu.edu.cn.
  • 6 Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Key Laboratory of Regenerative Medicine, Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
PMID: 40037209 DOI: 10.1016/j.biomaterials.2025.123210
Abstract

Osteoarthritis (OA) is a type of joint disease that influences millions of individuals. Regrettably, effective treatment for OA is currently unavailable. The challenge lies in the deep location of chondrocytes within the dense cartilage matrix that hinders the delivery and efficiency of clinical OA drugs. To overcome this obstacle, the present study proposed a hybrid nanodrug by Zinc(II) metal-drug coordination-driven self-assembly as highly efficient delivery system. This nano-assembly formulations possessed the ability to deliver two types of drugs, namely metformin (Met) and therapeutic genes (p65 siRNA). Results showed that this nano-assembly not only exhibited positive charge-driven anchoring to the cartilage matrix and effective drug delivery capacity, but also synergistically inhibited NF-κB activity and activates Autophagy of OA chondrocytes, thus safeguarding the cartilage. The successful achievement of this project not only contribute to the advancement of research on bio-nanomaterials for treating OA, but also establish a robust theoretical foundation for realizing promising and functional integration of nanomedicine targeting OA.

Keywords

Autophagy; Metformin; Nanodrugs; Osteoarthritis; siRNA.

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