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Self-Assembled Water-Soluble Nanofibers Displaying Collagen Hybridizing Peptides
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2017-11-13 00:00:00 , DOI: 10.1021/jacs.7b07900
Boi Hoa San 1 , Jeongmin Hwang 1 , Sujatha Sampath 1 , Yang Li 1 , Lucas L. Bennink 1 , S. Michael Yu 1, 2
Affiliation  

Collagen hybridizing peptides (CHP) have been demonstrated as a powerful vehicle for targeting denatured collagen (dColl) produced by disease or injury. Conjugation of β-sheet peptide motif to the CHP results in self-assembly of nonaggregating β-sheet nanofibers with precise structure. Due to the molecular architecture of the nanofibers which puts high density of hydrophilic CHPs on the nanofiber surface at fixed distance, the nanofibers exhibit high water solubility, without any signs of intramolecular triple helix formation or fiber–fiber aggregation. Other molecules that are flanked with the triple helical forming GlyProHyp repeats can readily bind to the nanofibers by triple helical folding, allowing facile display of bioactive molecules at high density. In addition, the multivalency of CHPs allows the nanofibers to bind to dColl in vitro and in vivo with extraordinary affinity, particularly without preactivation that unravels the CHP homotrimers. The length of the nanofibers can be tuned from micrometers down to 100 nm by simple heat treatment, and when injected intravenously into mice, the small nanofibers can specifically target dColl in the skeletal tissues with little target-associated signals in the skin and other organs. The CHP nanofibers can be a useful tool for detecting and capturing dColl, understanding how ECM remodelling impacts disease progression, and development of new delivery systems that target such diseases.

中文翻译:

显示胶原杂交肽的自组装水溶性纳米纤维

胶原蛋白杂交肽(CHP)已被证明是靶向疾病或损伤产生的变性胶原蛋白(dColl)的强大载体。β-折叠肽基序与CHP的缀合导致具有精确结构的非聚集β-折叠纳米纤维的自组装。由于纳米纤维的分子结构使亲水性CHP在固定距离处具有高密度的亲水性CHP,因此纳米纤维显示出高水溶性,没有任何分子内三螺旋形成或纤维-纤维聚集的迹象。与三螺旋形成的GlyProHyp重复序列侧翼的其他分子可以通过三螺旋折叠容易地结合至纳米纤维,从而以高密度容易地展示生物活性分子。此外,CHP的多价性使纳米纤维能够在体外和体内以非凡的亲和力与dColl结合,特别是无需预先激活即可解散CHP同型三聚体。纳米纤维的长度可以通过简单的热处理从微米调整到100 nm,当静脉内注射到小鼠体内时,小的纳米纤维可以特异性地靶向骨骼肌组织中的dColl,而皮肤和其他器官中几乎没有与靶标相关的信号。CHP纳米纤维可以成为检测和捕获dColl,了解ECM重塑如何影响疾病进展以及开发针对此类疾病的新型递送系统的有用工具。纳米纤维的长度可以通过简单的热处理从微米调整到100 nm,当静脉内注射到小鼠体内时,小的纳米纤维可以特异性地靶向骨骼肌组织中的dColl,而皮肤和其他器官中几乎没有与靶标相关的信号。CHP纳米纤维可以成为检测和捕获dColl,了解ECM重塑如何影响疾病进展以及开发针对此类疾病的新型递送系统的有用工具。纳米纤维的长度可以通过简单的热处理从微米调整到100 nm,当静脉内注射到小鼠体内时,小的纳米纤维可以特异性地靶向骨骼肌组织中的dColl,而皮肤和其他器官中几乎没有与靶标相关的信号。CHP纳米纤维可以成为检测和捕获dColl,了解ECM重塑如何影响疾病进展以及开发针对此类疾病的新型递送系统的有用工具。
更新日期:2017-11-16
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