Protease Degradation of Protein Coronas and Its Impact on Cancer Cells and Drug Payload Release
Protease Degradation of Protein Coronas and Its Impact on Cancer Cells and Drug Payload Release
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DOI：
10.1021/acsami.9b00928
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发表时间：
2019-04-24
影响因子：
9.5
通讯作者：
Hamad-Schifferli, Kimberly
中科院分区：
文献类型：
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作者：
Rodriguez-Quijada, Cristina;de Puig, Helena;Hamad-Schifferli, Kimberly
研究了基质金属蛋白酶（MMPs）对球形金纳米颗粒（AuNPs）周围预形成的蛋白质冠的影响。不同组成的蛋白质冠（人血清，人血清白蛋白，和胶原蛋白IV）周围的金纳米粒子形成和表征。蛋白酶MMP-9对电晕的影响取决于电晕的组成，导致电晕流体动力学直径（DH）的不同变化。当与PANC-1细胞孵育时，冠显示DH增加和减少的证据。改变冠的组成影响MMP-9的活性。此外，冠不仅受到MMP-9的蛋白酶活性的影响，而且还受到其与预先形成的冠中的蛋白质交换的能力的影响。这种交换也可能发生在培养基中的蛋白质上。因此，MMP-9的净效应是MMP-9蛋白酶活性和交换的组合。交换的时间尺度根据组成蛋白质冠的性质（弱结合冠蛋白与强结合冠蛋白）而变化。质谱法用于探测蛋白质冠组成，并支持交换和降解模型。总之，这些结果表明蛋白酶活性对AuNP冠的机制涉及重排和交换，然后降解。
The effect of matrix metalloproteinases (MMPs) on preformed protein coronas around spherical gold nanoparticles (AuNPs) was studied. Protein coronas of different compositions (human serum, human serum albumin, and collagen IV) were formed around AuNPs and characterized. The protease MMP-9 had different effects on the corona depending on the corona composition, resulting in different changes to the corona hydrodynamic diameter (DH). When incubated with PANC-1 cells, the corona showed evidence of both increases as well as decreases in DH. Varying the composition of the corona influenced the MMP-9 activity. Furthermore, the corona was influenced not only by the protease activity of the MMP-9 but also by its ability to exchange with proteins in the preformed corona. This exchange could also occur with proteins in the media. Thus, the net effect of the MMP-9 was a combination of the MMP-9 protease activity and also exchange. Time scales for the exchange varied depending on the nature that make up the protein corona (weakly vs strongly bound corona proteins). Mass spectrometry was used to probe the protein corona composition and supported the exchange and degradation model. Together, these results indicate that the mechanism of protease activity on AuNP coronas involves both rearrangement and exchange, followed by degradation.