Ultra-small superparamagnetic iron oxide nanoparticles for intra-articular targeting of cartilage in early osteoarthritis

Jun Wu; Changqiang Wu; Zhongyuan Cai; Haojie Gu; Li Liu; Chunchao Xia; Su Lui; Qiyong Gong; Bin Song; Hua Ai

doi:10.1093/rb/rbad052

Ultra-small superparamagnetic iron oxide nanoparticles for intra-articular targeting of cartilage in early osteoarthritis

Regen Biomater. 2023 May 11:10:rbad052. doi: 10.1093/rb/rbad052. eCollection 2023.

Authors

Jun Wu^{1

2}, Changqiang Wu², Zhongyuan Cai³, Haojie Gu³, Li Liu³, Chunchao Xia⁴, Su Lui⁴, Qiyong Gong^{5

6

7}, Bin Song^{4

8}, Hua Ai^{3

4}

Affiliations

¹ Institute for Disaster Management and Reconstruction, Sichuan University, Chengdu 610207, China.
² Medical Imaging Key Laboratory of Sichuan Province, School of Medical Imaging, North Sichuan Medical College, Nanchong 637000, China.
³ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
⁴ Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ Department of Radiology, Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
⁶ Functional and Molecular Imaging Key Laboratory of Sichuan Province, Key Laboratory of Transplant Engineering and Immunology, NHC, Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610064, China.
⁷ Department of Radiology, West China Xiamen Hospital of Sichuan University, Fujian, Xiamen 361000, China.
⁸ Department of Radiology, Sanya People's Hospital, Hainan, Sanya 572000, China.

Abstract

Early diagnosis of osteoarthritis (OA) is critical for effective cartilage repair. However, lack of blood vessels in articular cartilage poses a barrier to contrast agent delivery and subsequent diagnostic imaging. To address this challenge, we proposed to develop ultra-small superparamagnetic iron oxide nanoparticles (SPIONs, 4 nm) that can penetrate into the matrix of articular cartilage, and further modified with the peptide ligand WYRGRL (particle size, 5.9 nm), which allows SPIONs to bind to type II collagen in the cartilage matrix and increase the retention of probes. Type II collagen in the cartilage matrix is gradually lost with the progression of OA, consequently, the binding of peptide-modified ultra-small SPIONs to type II collagen in the OA cartilage matrix is less, thus presenting different magnetic resonance (MR) signals in OA group from the normal ones. By introducing the AND logical operation, damaged cartilage can be differentiated from the surrounding normal tissue on T1 and T2 AND logical map of MR images, and this was also verified in histology studies. Overall, this work provides an effective strategy for delivering nanosized imaging agents to articular cartilage, which could potentially be used to diagnosis joint-related diseases such as osteoarthritis.

Keywords: collagen type II; early osteoarthritis; magnetic resonance imaging; superparamagnetic iron oxide; targeting peptide.