Results
Title

Phosphatidylserine‐Incorporated Exosome Mimetics Encapsulating CXCR3 Antagonist Alleviate Osteoporosis.

Authors

Kang, Minjee; Li, Zhi; Chang, Insoon; Xu, Changlu; Chiang, Michelle; Kim, Lauren; Wu, Yutong; Fan, Jiabing; Aghaloo, Tara; Lee, Min

Abstract

Exosomes 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.

Subjects

EXTRACELLULAR vesicles; MESENCHYMAL stem cells; MEMBRANE lipids; DRUG delivery systems; BONE resorption; CHEMOKINE receptors

Publication

Advanced Functional Materials, 2024, Vol 34, Issue 38, p1

ISSN

1616-301X

Publication type

Academic Journal

DOI

10.1002/adfm.202402521