Biomimetic Design of Protein Nanomaterials for Hydrophobic Molecular Transport.
Biomimetic Design of Protein Nanomaterials for Hydrophobic Molecular Transport.
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DOI：
10.1002/adfm.201200052
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发表时间：
2012-08-07
影响因子：
19
通讯作者：
Wang, Szu-Wen
中科院分区：
文献类型：
--
作者：
Ren, Dongmei;Dalmau, Merce;Randall, Arlo;Shindel, Matthew M.;Baldi, Pierre;Wang, Szu-Wen
自组装生物复合物等生物材料在材料科学和纳米技术中有着广泛的应用。然而，基于蛋白质的材料的功能性通常受到特定化学缀合位点的缺乏或位置的限制。在这项研究中，我们开发了一种新的策略，用于将有机分子装载到仅依赖于非共价相互作用的蛋白质纳米颗粒的空腔中，并且我们证明了其在药物递送中的适用性。基于一个仿生模型，将多个苯丙氨酸创建一个广义的结合位点，我们保留和交付的抗肿瘤化合物阿霉素通过重新设计的笼蛋白支架。通过结构建模和蛋白质工程的迭代结合，我们获得了具有不同水平载药能力的丙酮酸脱氢酶E2亚基的新变体。我们发现，越来越多的引入支架腔内的苯丙氨酸通常会导致更大的载药能力。可以实现大于常规纳米颗粒递送系统的药物负载水平。这些含有阿霉素的蛋白质纳米颗粒被乳腺癌细胞吸收并诱导显著的细胞死亡。我们的新方法展示了一种通用的策略，在基于蛋白质的支架内设计从头疏水结合结构域，用于分子封装和运输，并且它拓宽了将客体分子连接到这类材料的能力。
Biomaterials such as self-assembling biological complexes have demonstrated a variety of applications in materials science and nanotechnology. The functionality of protein-based materials, however, is often limited by the absence or locations of specific chemical conjugation sites. In this investigation, we developed a new strategy for loading organic molecules into the hollow cavity of a protein nanoparticle that relies only on non-covalent interactions, and we demonstrated its applicability in drug delivery. Based on a biomimetic model that incorporates multiple phenylalanines to create a generalized binding site, we retained and delivered the antitumor compound doxorubicin by redesigning a caged protein scaffold. Through an iterative combination of structural modeling and protein engineering, we obtained new variants of the E2 subunit of pyruvate dehydrogenase with varying levels of drug-carrying capabilities. We found that an increasing number of introduced phenylalanines within the scaffold cavity generally resulted in greater drug loading capacities. Drug loading levels could be achieved that were greater than conventional nanoparticle delivery systems. These protein nanoparticles containing doxorubicin were taken up by breast cancer cells and induced significant cell death. Our novel approach demonstrates a universal strategy to design de novo hydrophobic binding domains within protein-based scaffolds for molecular encapsulation and transport, and it broadens the ability to attach guest molecules to this class of materials.
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影响因子：
2.9
作者：
JACKSON, SE;MORACCI, M;FERSHT, AR
通讯作者：
FERSHT, AR
影响因子：
7.3
作者：
Gannon MK 2nd;Holt JJ;Bennett SM;Wetzel BR;Loo TW;Bartlett MC;Clarke DM;Sawada GA;Higgins JW;Tombline G;Raub TJ;Detty MR
通讯作者：
Detty MR
影响因子：
5.8
作者：
Formariz, T. R.;Sarmento, V. H. V.;Oliveira, A. G.
通讯作者：
Oliveira, A. G.
影响因子：
5
作者：
Castro, GR;Larson, BK;Kaplan, DL
通讯作者：
Kaplan, DL
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.