Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; pp. 220 - 23
• Main Authors: Zheng, Gang, Ma, Hai-Wei, Xiang, Guang-Heng, He, Gao-Lu, Cai, Han-Chen, Dai, Zi-Han, Chen, Yan-Lin, Lin, Yan, Xu, Hua-Zi, Ni, Wen-Fei, Xu, Cong, Liu, Hai-Xiao, Wang, Xiang-Yang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31.10.2022; BioMed Central; BMC
• Subjects: Alendronate - pharmacology; Angiogenesis; Arthritis; Blood products; Bone-targeting; Bones; Care and treatment; Cell organelles; Complications and side effects; Corticosteroids; Drug delivery systems; Exosome; Exosomes; Exosomes - metabolism; Glucocorticoid; Glucocorticoids; Glucocorticoids - metabolism; Health aspects; Humans; Medical research; Medicine, Experimental; Mesenchymal Stem Cells - metabolism; Morphology; Nanomedicine; Osteogenesis; Osteoporosis; Osteoporosis - chemically induced; Osteoporosis - drug therapy; Platelet lysate; Proteins; Tumorigenesis; Vascular endothelial growth factor; China; Bone-targeting; Osteoporosis; Platelet lysate; Exosome; Glucocorticoid
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01400-1

Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.