Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, USA.
Aiiso Yufeng Li Family Department of Chemical and NanoEngineering, University of California San Diego, La Jolla, CA, USA.
Nat Commun. 2024 Aug 24;15(1):7295. doi: 10.1038/s41467-024-51218-8.
Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.
无膜凝聚物的稳定性问题已经通过涂层策略得到解决，但这些方法往往会损害凝聚物的通透性。在这里，我们报告了一种使用单宁酸来保持稳定性和通透性的简便方法，然后在酶触发药物释放中展示了这种方法的价值。首先，我们通过肝素糖胺聚糖与酪氨酸和精氨酸基肽自组装来开发尺寸可调的凝聚物。肽结构单元中的凝血酶识别位点导致肝素在凝血酶蛋白水解时释放。值得注意的是，多酚整合在纳米凝聚物中，以提高在生物流体中的稳定性。多酚在液-液相界面交联，使纳米凝聚物在各种环境中保持出色的结构完整性。我们发现了一个关键的多酚阈值，既能保持酶活性，又能增强稳定性。纳米凝聚物的解体速率随凝血酶活性的增加而增加，从而防止凝血级联反应。这种基于多酚的方法不仅提高了稳定性，而且为在生物医学、蛋白酶传感和生物响应性药物输送中的应用开辟了道路。
