Department of Biomedical Engineering, 1098 Research Transition Facility, University of Alberta, 8308-114 Street, Edmonton, AB, T6G 2V2, Canada.
Faculty of Pharmacy and Pharmaceutical Sciences, 2-35B Medical Sciences Building, University of Alberta, Edmonton, AB, T6G 2H1, Canada.
J Nanobiotechnology. 2018 Feb 17;16(1):15. doi: 10.1186/s12951-018-0342-5.
Elastin-like polypeptides (ELPs) are a fascinating biomaterial that has undergone copious development for a variety of therapeutic applications including as a nanoscale drug delivery vehicle. A comprehensive understanding of ELP self-assembly is lacking and this knowledge gap impedes the advancement of ELP-based biomaterials into the clinical realm. The systematic examination of leucine-containing ELPs endeavors to expand existing knowledge about fundamental assembly-disassembly behaviours.
It was observed that these marginally soluble, short ELPs tend to behave consistently with previous observations related to assembly-related ELP phase transitions but deviated in their disassembly. It was found that chain length, concentration and overall sequence hydrophobicity may influence the irreversible formation of sub-micron particles as well as the formation of multi-micron scale, colloidally unstable aggregates. Amino acid composition affected surface charge and packing density of the particles. Particle stability upon dilution was found to vary depending upon chain length and hydrophobicity, with particles composed of longer and/or more hydrophobic ELPs being more resistant to disassembly upon isothermal dilution.
Taken together, these results suggest marginally soluble ELPs may self-assemble but not disassemble as expected and that parameters including particle size, zeta potential and dilution resistance would benefit from widespread systematic evaluations. This information has the potential to reveal novel preparation methods capable of expanding the utility of all existing ELP-based biomaterials.
弹性蛋白样多肽（ELPs）是一种引人入胜的生物材料，已经经过大量开发，可用于多种治疗应用，包括作为纳米级药物输送载体。对 ELP 自组装的全面了解还很缺乏，这一知识差距阻碍了基于 ELP 的生物材料进入临床领域。对含亮氨酸的 ELP 的系统研究旨在扩展关于基本组装-拆卸行为的现有知识。
观察到这些溶解度较低的短 ELP 倾向于表现出与以前关于与组装相关的 ELP 相转变相关的观察结果一致，但在其拆卸中存在偏差。发现链长、浓度和整体序列疏水性可能影响亚微米颗粒的不可逆形成以及多微米尺度的胶体不稳定聚集体的形成。氨基酸组成影响颗粒的表面电荷和堆积密度。发现稀释后颗粒的稳定性取决于链长和疏水性，由较长和/或疏水性 ELP 组成的颗粒在等温稀释时更能抵抗拆卸。
综上所述，这些结果表明，溶解度较低的 ELP 可能会自组装但不会像预期的那样拆卸，并且包括粒径、Zeta 电位和稀释阻力在内的参数将受益于广泛的系统评估。这些信息有可能揭示出新颖的制备方法，从而扩大所有现有基于 ELP 的生物材料的应用。
