Phosphatidylserine‐Incorporated Exosome Mimetics Encapsulating CXCR3 Antagonist Alleviate Osteoporosis

Author:

Kang Minjee1ORCID,Li Zhi1,Chang Insoon2,Xu Changlu1,Chiang Michelle1,Kim Lauren1,Wu Yutong3,Fan Jiabing4,Aghaloo Tara5,Lee Min16ORCID

Affiliation:

1. Division of Oral and Systemic Health Sciences School of Dentistry University of California Los Angeles CA 90095 USA

2. Division of Regenerative and Reconstructive Sciences School of Dentistry University of California Los Angeles CA 90095 USA

3. Department of Chemistry and Biochemistry University of California Los Angeles CA 90095 USA

4. Department of Pharmaceutical Sciences School of Pharmacy and Health Professions University of Maryland Eastern Shore Princess Anne Maryland 21853 USA

5. Division of Diagnostic and Surgical Sciences School of Dentistry University of California Los Angeles CA 90095 USA

6. Department of Bioengineering University of California, Los Angeles Los Angeles CA 90095 USA

Abstract

AbstractExosomes derived from mesenchymal stem cells are an active area of research due to their therapeutic potential in treating osteoporosis. To further harness their therapeutic performance in modulating bone resorption, equipped exosomes with osteoclast‐targeting moieties on their surface as well as chemokine receptor antagonists blocking osteoclast recruitment. Phosphatidylserine (PS), a membrane lipid exerting immunosuppressive and phagocytic signals, is incorporated in the membrane of exosome mimetics (EMs) to achieve a marked affinity for osteoclast precursors and potential anti‐resorptive effects. This is also aimed to tackle a CXCL9‐CXCR3 ligand‐receptor axis, a critical signaling axis in regulating osteoclast precursor recruitment and differentiation at bone resorption sites, by encapsulating a chemical antagonist of CXCR3, AMG487, in the PS‐incorporated EMs (PS‐EMs). The osteoclast‐targeting PS‐EMs loaded with AMG487 effectively protected against bone loss in an ovariectomized mouse model. These findings demonstrate the great promise of PS‐EMs as anti‐resorptive nanotherapies for alleviating osteoporosis.

Funder

U.S. Department of Defense

National Institutes of Health

Publisher

Wiley

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