Jung Se-Hui, Choi Joung-Woo, Yun Chae-Ok, Kim Sun Hwa, Kwon Ick Chan, Ghandehari Hamidreza
†Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea.
‡Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
Mol Pharm. 2015 May 4;12(5):1673-9. doi: 10.1021/acs.molpharmaceut.5b00075. Epub 2015 Apr 22.
Silk-elastinlike protein polymer (SELP) hydrogels have been investigated for sustained local delivery of adenoviral gene carriers to solid tumors. These polymers degrade in the presence of proteases such as elastase. A detailed understanding of the interaction of SELPs with viruses and their degradation in the presence of elastase can provide useful information about mechanisms of sustained gene delivery from these systems. In this work, we investigated the interactions of SELPs with adenoviruses (Ads) and elastase using atomic force microscopy. We observed that viral particles interacted strongly with SELP networks formed by cross-linking of nanofibers. The presence of viruses contributed to enhanced network formation. Incubation of Ad with SELPs in the liquid state induced close packing of the viral colony. Morphological changes of SELP networks cleaved by enzymatic interaction with elastase were investigated. SELP-415K fiber networks were more responsive to temperature changes and were slowly degraded by elastases compared to SELP-47K, a SELP analogue with shorter elastin units in the monomer repeat. These studies provide insight into the influence of SELP structure on degradation and potential mechanisms of increased viral stability.
丝素弹性蛋白样蛋白聚合物（SELP）水凝胶已被用于研究向实体瘤持续局部递送腺病毒基因载体。这些聚合物在诸如弹性蛋白酶等蛋白酶存在的情况下会降解。详细了解SELP与病毒的相互作用以及它们在弹性蛋白酶存在下的降解情况，可为这些系统的持续基因递送机制提供有用信息。在这项工作中，我们使用原子力显微镜研究了SELP与腺病毒（Ads）和弹性蛋白酶的相互作用。我们观察到病毒颗粒与由纳米纤维交联形成的SELP网络强烈相互作用。病毒的存在有助于增强网络形成。在液态下将腺病毒与SELP孵育会导致病毒菌落紧密堆积。研究了与弹性蛋白酶发生酶促相互作用而裂解的SELP网络的形态变化。与SELP-47K（一种在单体重复序列中具有较短弹性蛋白单元的SELP类似物）相比，SELP-415K纤维网络对温度变化更敏感，并且被弹性蛋白酶缓慢降解。这些研究深入了解了SELP结构对降解的影响以及病毒稳定性增加的潜在机制。
