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

    Journal: J. Nanobiotechnol., Volume 20, OCT 31

    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

    Organizations: National Natural Science Foundation of China [81871806]; Wenzhou Science and Technology Bureau Foundation [ZY2019014]; Zhejiang Provincial Natural Science Foundation of China [LY21H060009]

    Keywords: Glucocorticoid; Osteoporosis; Platelet lysate; Exosome; Bone-targeting

    Background: 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. Results: 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. Conclusions: 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.
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