Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design.
Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design.
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DOI：
10.1021/acsnano.8b07401
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发表时间：
2019-01
期刊：
影响因子：
17.1
通讯作者：
Jiye Son;Daniela Kalafatovic;Mohit Kumar;B. Yoo;Mike A. Cornejo;M. Contel;R. Ulijn
中科院分区：
文献类型：
--
作者：
Jiye Son;Daniela Kalafatovic;Mohit Kumar;B. Yoo;Mike A. Cornejo;M. Contel;R. Ulijn
基质金属蛋白酶-9（MMP-9）的过度表达和活化与多种疾病相关，并且可以作为刺激物来活化纳米材料以用于传感和控制释放。为了实现具有改进的时空靶向能力的自主治疗，除了将酶可切割的接头引入纳米结构中之外，还需要考虑几个特征。我们介绍了一个可定制的平台，使用超分子肽纳米结构与三个模块化组件，以实现可调的动力学和形态学变化后，MMP-9曝光的指导原则。这种方法能够实现（1）通过引入有序/无序结构来微调动力学，（2）通过颗粒和酶电荷的静电（错误）匹配实现水解速率的12倍变化，以及（3）选择是细胞杀伤纳米纤维或崩解的酶促反应产物。这些指导原则，可以合理化，并涉及几个氨基酸的交换，使酶响应肽纳米结构的系统定制，一般用于酶响应材料的性能优化。
Overexpression and activation of matrix metalloproteinase-9 (MMP-9) is associated with multiple diseases and can serve as a stimulus to activate nanomaterials for sensing and controlled release. In order to achieve autonomous therapeutics with improved space-time targeting capabilities, several features need to be considered beyond the introduction of an enzyme-cleavable linker into a nanostructure. We introduce guiding principles for a customizable platform using supramolecular peptide nanostructures with three modular components to achieve tunable kinetics and morphology changes upon MMP-9 exposure. This approach enables (1) fine-tuning of kinetics through introduction of ordered/disordered structures, (2) a 12-fold variation in hydrolysis rates achieved by electrostatic (mis)matching of particle and enzyme charge, and (3) selection of enzymatic reaction products that are either cell-killing nanofibers or disintegrate. These guiding principles, which can be rationalized and involve exchange of just a few amino acids, enable systematic customization of enzyme-responsive peptide nanostructures for general use in performance optimization of enzyme-responsive materials.