Engineering nanocages with polyglutamate domains for coupling to hydroxyapatite biomaterials and allograft bone.
Engineering nanocages with polyglutamate domains for coupling to hydroxyapatite biomaterials and allograft bone.
复制标题
用聚谷氨酸结构域的工程纳米范围与羟基磷灰石生物材料和同种异体移植骨偶联。
DOI：
10.1016/j.biomaterials.2012.12.026
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发表时间：
2013-03
期刊：
影响因子：
14
通讯作者：
Bellis, Susan L.
中科院分区：
文献类型：
--
作者：
Culpepper, Bonnie K.;Morris, David S.;Prevelige, Peter E.;Bellis, Susan L.
羟基磷灰石(HA)是骨矿物的主要成分，人工合成HA被广泛用作骨修复的生物材料。以往的工作表明，聚谷氨酸结构域可以选择性地与HA结合，这些结构域可以用来将生物活性多肽偶联到许多不同的含HA材料上。在目前的研究中，我们采用了这项技术来将多个谷氨酸结构域改造成来自P22噬菌体的载货纳米笼结构。P22纳米笼由于其稳定性、大容量负载多种蛋白质和其他类型的货物，以及抵抗蛋白酶降解的能力，已显示出作为药物输送系统的巨大潜力。用定点突变的方法修改P22外壳蛋白的初级编码序列，使其包含富含谷氨酸的区域。与野生型P22相比，聚谷氨酸修饰的纳米笼(E2-P22)与陶瓷羟基磷灰石、微粒羟基磷灰石和同种异体骨的结合力增强。此外，E2-P22的结合是HA选择性的，这从纳米笼与非HA材料(包括聚苯乙烯、琼脂和聚己内酯(PCL))的结合可以忽略不计。综上所述，这些结果建立了一种新的机制，将纳米笼药物输送系统定向偶联到各种骨疗法中常用的各种含有HA的材料上。
Hydroxyapatite (HA) is the principal constituent of bone mineral, and synthetic HA is widely used as a biomaterial for bone repair. Previous work has shown that polyglutamate domains bind selectively to HA and that these domains can be utilized to couple bioactive peptides onto many different HA-containing materials. In the current study we have adapted this technology to engineer polyglutamate domains into cargo-loaded nanocage structures derived from the P22 bacteriophage. P22 nanocages have demonstrated significant potential as a drug delivery system due to their stability, large capacity for loading with a diversity of proteins and other types of cargo, and ability to resist degradation by proteases. Site-directed mutagenesis was used to modify the primary coding sequence of the P22 coat protein to incorporate glutamate-rich regions. Relative to wild-type P22, the polyglutamate-modified nanocages (E2-P22) exhibited increased binding to ceramic HA disks, particulate HA and allograft bone. Furthermore, E2-P22 binding was HA selective, as evidenced by negligible binding of the nanocages to non-HA materials including polystyrene, agarose, and polycaprolactone (PCL). Taken together these results establish a new mechanism for the directed coupling of nanocage drug delivery systems to a variety of HA-containing materials commonly used in diverse bone therapies.
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影响因子：
14
作者：
Culpepper, Bonnie K.;Bonvallet, Paul P.;Reddy, Michael S.;Ponnazhagan, Selvarangan;Bellis, Susan L.
通讯作者：
Bellis, Susan L.
影响因子：
14
作者：
Cenni, Elisabetta;Granchi, Donatella;Baldini, Nicola
通讯作者：
Baldini, Nicola
影响因子：
6.2
作者：
Kasugai, S;Fujisawa, R;Ohya, K
通讯作者：
Ohya, K
影响因子：
2.9
作者：
Lanman, J;Tuma, R;Prevelige, PE
通讯作者：
Prevelige, PE
DOI：
10.1007/s11420-005-0111-5
发表时间：
2005-09-01
期刊：
HSS journal : the musculoskeletal journal of Hospital for Special Surgery
影响因子：
--
作者：
Bostrom, Mathias P G;Seigerman, Daniel A
通讯作者：
Seigerman, Daniel A