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A cell surface clicked navigation system to direct specific bone targeting
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2017-12-26 , DOI: 10.1016/j.bmc.2017.12.037
Young Kim , Zhe Zhang , Jae-Hyuck Shim , Tae Sup Lee , Ching-Hsuan Tung

Cell therapies are promising up-and-coming therapeutic strategies for many diseases. For maximal therapeutic benefits, injected cells have to navigate their way to a designated area, including organ and tissue; unfortunately, the majority of therapeutic cells are currently administered without a guide or homing device. To improve this serious shortcoming, a functionalization method was developed to equip cells with a homing signal. Its application was demonstrated by applying an Azadibenzocyclooctyne-bisphosphonate (ADIBO-BP) and azide paired bioorthogonal chemistry on cells for bone specific homing. Jurkat T cells and bone marrow derived stromal cells (BMSCs) were cultured with tetraacetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz) to place unnatural azido groups onto the cell’s surface; these azido groups were then reacted with ADIBO-BP. The tethered bisphosphonates were able to bring Jurkat cells to hydroxyapatite, the major component of bone, and mineralized SAOS-2 cells. The incorporated BP groups also enhanced the specific affinity of BMSCs to mouse femur bone fragments in vitro. The introduced navigation strategy is expected to have a broad application in cell therapy, because through the biocompatible ADIBO and azide reactive pair, various homing signals could be efficiently anchored onto therapeutic cells.



中文翻译:

细胞表面点击导航系统可指导特定的骨骼定位

细胞疗法是针对许多疾病的有前途的新兴治疗策略。为了获得最大的治疗效果,注射的细胞必须导航到指定区域,包括器官和组织;不幸的是,目前大多数治疗细胞是在没有引导或归巢装置的情况下施用的。为了改善这个严重的缺点,开发了一种功能化方法来为细胞配备归巢信号。通过将Azadibenzocyclooctyne-bisphosphonate(ADIBO-BP)和叠氮化物配对生物正交化学应用于细胞进行骨特异性归巢,证明了其应用。Jurkat T细胞和骨髓衍生的基质细胞(BMSCs)与四乙酰化中培养Ñ -azidoacetyl- d -mannosamine(AC 4ManNAz)将不自然的叠氮基团置于细胞表面;然后将这些叠氮基与ADIBO-BP反应。束缚的双膦酸盐能够将Jurkat细胞带入骨骼的主要成分羟基磷灰石和矿化的SAOS-2细胞。并入的BP基团还在体外增强了BMSC对小鼠股骨片段的特异性亲和力。引入的导航策略有望在细胞治疗中得到广泛应用,因为通过生物相容性ADIBO和叠氮化物反应对,各种归巢信号可以有效地锚定在治疗细胞上

更新日期:2017-12-26
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