Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.
Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.
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DOI：
10.1002/adma.201701255
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Murphy WL
中科院分区：
文献类型：
--
作者：
Yu X;Biedrzycki AH;Khalil AS;Hess D;Umhoefer JM;Markel MD;Murphy WL
蛋白质在配制、储存和递送过程中由于其脆弱的结构构象而趋于失去其生物活性。因此，不能稳定控释系统中的蛋白质代表了药物递送中的主要障碍。在这里，我们提出了一种骨矿物质启发的蛋白质稳定化策略，它在医疗器械上使用纳米结构的矿物涂层。结合在纳米结构涂层内的蛋白质表现出增强的稳定性，对极端的外部压力，包括有机溶剂，蛋白酶和环氧乙烷气体灭菌。蛋白质的稳定效果归因于蛋白质构象结构的维持，这与矿物涂层的纳米级特征尺寸密切相关。从纳米结构矿物涂层释放的碱性成纤维细胞生长因子（bFGF）在释放期间保持其生物活性数周，而在从常用聚合物微球释放期间保持活性少于7天。使用矿物涂层外科缝线输送生长因子bFGF和血管内皮生长因子（VEGF）显著改善了兔模型中的功能性跟腱愈合，导致血管形成增加，胶原纤维组织更成熟，机械性能提高2倍。我们的研究结果表明，蛋白质和纳米结构矿物之间的仿生相互作用提供了一种新的，广泛适用的机制，以稳定蛋白质的药物输送和再生医学的背景下。
Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here we present a bone mineral inspired protein stabilization strategy, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrated enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect was attributed to the maintenance of protein conformational structure, which was closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintained its biological activity for weeks during release, while it maintained activity for less than seven days during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor (VEGF) using a mineral coated surgical suture significantly improved functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a 2-fold improvement in mechanical properties. Our findings demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine.
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影响因子：
14
作者：
Suarez-Gonzalez, Darilis;Barnhart, Kara;Migneco, Francesco;Flanagan, Colleen;Hollister, Scott J.;Murphy, William L.
通讯作者：
Murphy, William L.
影响因子：
2.8
作者：
Schmidt-Schultz, TH;Schultz, M
通讯作者：
Schultz, M
影响因子：
64.8
作者：
Jeong, B;Bae, YH;Kim, SW
通讯作者：
Kim, SW
影响因子：
29.4
作者：
Jongpoiboonkit, Leenaporn;Franklin-Ford, Travelle;Murphy, William L.
通讯作者：
Murphy, William L.
影响因子：
3.7
作者：
Schmidt-Schultz, TH;Schultz, M
通讯作者：
Schultz, M