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Tissue adhesive FK506–loaded polymeric nanoparticles for multi–layered nano–shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model
Biomaterials ( IF 12.8 ) Pub Date : 2017-11-01 , DOI: 10.1016/j.biomaterials.2017.10.049
Tung Thanh Pham , Tiep Tien Nguyen , Shiva Pathak , Shobha Regmi , Hanh Thuy Nguyen , Tuan Hiep Tran , Chul Soon Yong , Jong Oh Kim , Pil–Hoon Park , Min Hui Park , Young Kyung Bae , Jeong Uk Choi , Youngro Byun , Cheol–Hee Ahn , Simmyung Yook , Jee–Heon Jeong

This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4–dihydroxyl–l–phenylalanine (DOPA) conjugated poly(lactide–co–glycolide)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (DOPA–NPs) carrying immunosuppressant FK506 (FK506/DOPA–NPs). The functionalized DOPA–NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co–culture condition with xenogenic lymphocytes for 7 days. Interestingly, the mean survival time of islets coated with FK506/DOPA–NPs was significantly higher as compared with that of islets coated with DOPA–NPs (without FK506) and control. This study demonstrated that the combination of surface camouflage and localized low dose of immunosuppressant could be an effective approach in prolonging the survival of transplanted islets. This newly developed platform might be useful for immobilizing various types of small molecules on therapeutic cells and biomaterial surface to improve the therapeutic efficacy in cell therapy and regenerative medicine.

中文翻译:

组织粘合剂FK506负载的聚合物纳米颗粒用于胰腺胰岛的多层纳米屏蔽,以增强糖尿病小鼠模型的异种移植存活率

这项研究旨在开发一种新的表面修饰技术,以在异种移植模型中延长胰岛的存活时间,使用3,4–二羟基–l–苯丙氨酸(DOPA)共轭的聚(丙交酯-共-乙交酯)-聚(乙烯)乙二醇(PLGA–PEG)纳米颗粒(DOPA–NPs)带有免疫抑制剂FK506(FK506 / DOPA–NPs)。功能化的DOPA-NPs形成了一种多功能的抗原迷彩涂层,而不会干扰胰岛的生存能力和功能。在与异种淋巴细胞共培养的条件下,该涂层有效地保存了胰岛的形态和存活力达7天。有趣的是,涂有FK506 / DOPA-NP的胰岛的平均存活时间明显高于涂有DOPA-NP(无FK506)和对照的胰岛的平均存活时间。这项研究表明,表面伪装和局部低剂量免疫抑制剂的组合可能是延长移植胰岛存活的有效方法。这个新开发的平台可能对将各种类型的小分子固定在治疗细胞和生物材料表面上有用,以提高细胞治疗和再生医学的治疗功效。
更新日期:2017-11-01
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