Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells

Yao Lu; Zhan Li; Lihua Li; Jieli Chen; Xingyi Xu; Zefeng Lin; Tao Zhang; Ye Zhu; Changhai Ding; Chuanbin Mao

doi:10.1016/j.biomaterials.2022.121474

Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells

Biomaterials. 2022 Apr:283:121474. doi: 10.1016/j.biomaterials.2022.121474. Epub 2022 Mar 18.

Authors

Yao Lu¹, Zhan Li², Lihua Li³, Jieli Chen⁴, Xingyi Xu³, Zefeng Lin², Tao Zhang², Ye Zhu⁵, Changhai Ding⁶, Chuanbin Mao⁷

Affiliations

¹ Clinical Research Center, Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; Guangdong Key Lab of Orthopedic Technology and Implant, Department of Orthopedics, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, 510010, China. Electronic address: oayul@smu.edu.cn.
² Guangdong Key Lab of Orthopedic Technology and Implant, Department of Orthopedics, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, 510010, China.
³ Department of Applied Physics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 999077, China.
⁴ Clinical Research Center, Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.
⁵ Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, 73019, USA.
⁶ Clinical Research Center, Department of Joint and Orthopedics, Orthopedic Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, 7000, Australia; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Southern Medical University, Guangzhou, 510630, China. Electronic address: changhai.ding@utas.edu.au.
⁷ Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, 73019, USA; School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027, PR China. Electronic address: maophage@gmail.com.

PMID: 35316662
DOI: 10.1016/j.biomaterials.2022.121474

Abstract

Traditional medication is not satisfied in rheumatoid arthritis (RA) therapy due to its long-term side effects and failure in cartilage repair. Nanomodification of mesenchymal stem cells (MSCs) holds promise for lifting such hurdles but delivering therapeutic nanomaterials (NPs) into MSCs remains challenging in this new strategy. Here, we show that CuS@MnO₂ NPs functionalized with a short phage-selected MSC-targeting peptide enabled the NPs to be uptaken by MSCs. The resultant NP-modified MSCs, further loaded with metformin, significantly improved stem cell therapy of RA. Specifically, the NP-modified MSCs survived the RA-associated oxidized stress through regulating the stress by the superoxide dismutase (SOD)- and catalase (CAT)-like activity of the NPs. They also exhibited an increased capability of cell migration, anti-inflammation, and chondrogenesis due to the nanomodification, thereby effectively inhibiting synovial inflammation and reducing cartilage erosion to relieve RA symptoms in two rat models 28 days post intravenous injection. Our peptide-promoted NP-modified MSCs may be used to enhance therapeutic effects in treating not only RA but also other degenerative and inflammatory diseases.

Keywords: Nanocatalysts; Phage-peptide; Rheumatoid arthritis; Stem cell therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arthritis, Rheumatoid* / therapy
Manganese Compounds
Mesenchymal Stem Cells* / physiology
Oxides
Peptides
Rats

Substances

Manganese Compounds
Oxides
Peptides