Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90033-9121, USA.
Biomacromolecules. 2012 Sep 10;13(9):2645-54. doi: 10.1021/bm300472y. Epub 2012 Aug 21.
Peptide amphiphiles (PAs) self-assemble nanostructures with potential applications in drug delivery and tissue engineering. Some PAs share environmentally responsive behavior with their peptide components. Here we report a new type of PAs biologically inspired from human tropoelastin. Above a lower critical solution temperature (LCST), elastin-like polypeptides (ELPs) undergo a reversible inverse phase transition. Similar to other PAs, elastin-like PAs (ELPAs) assemble micelles with fiber-like nanostructures. Similar to ELPs, ELPAs have inverse phase transition behavior. Here we demonstrate control over the ELPAs fiber length and cellular uptake. In addition, we observed that both peptide assembly and nanofiber phase separation are accompanied by a distinctive secondary structure attributed primarily to a type-1 β turn. We also demonstrate increased solubility of hydrophobic paclitaxel (PAX) in the presence of ELPAs. Due to their biodegradability, biocompatibility, and environmental responsiveness, elastin-inspired biopolymers are an emerging platform for drug and cell delivery; furthermore, the discovery of ELPAs may provide a new and useful approach to engineer these materials into stimuli-responsive gels and drug carriers.
肽两亲物（PAs）自组装成纳米结构，具有在药物输送和组织工程中的潜在应用。一些 PAs 具有与其肽成分一样的环境响应行为。在这里，我们报告了一种新型的 PAs，它是从人弹性蛋白中得到灵感的。在低于临界溶液温度（LCST）以上，弹性蛋白样多肽（ELPs）经历可逆的相反相转变。与其他 PAs 类似，弹性蛋白样 PAs（ELPAs）组装成具有纤维状纳米结构的胶束。与 ELPs 类似，ELPAs 具有相反的相转变行为。在这里，我们证明了对 ELPAs 纤维长度和细胞摄取的控制。此外，我们观察到，肽组装和纳米纤维相分离都伴随着一种独特的二级结构，主要归因于一种类型-1β 转角。我们还证明了在 ELPAs 存在的情况下，疏水性紫杉醇（PAX）的溶解度增加。由于其生物降解性、生物相容性和环境响应性，基于弹性蛋白的生物聚合物是药物和细胞输送的新兴平台；此外，ELPAs 的发现可能为将这些材料工程化为对刺激有响应的凝胶和药物载体提供一种新的、有用的方法。
