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Versatile Reversible Cross-Linking Strategy to Stabilize CCMV Virus Like Particles for Efficient siRNA Delivery.
Bioconjugate Chemistry ( IF 4.7 ) Pub Date : 2019-12-06 , DOI: 10.1021/acs.bioconjchem.9b00731
Chiara Pretto 1 , Jan C M van Hest 1
Affiliation  

Virus like particles obtained from the Cowpea Chlorotic Mottle Virus (CCMV) represent an innovative platform for drug delivery applications. Their unique reversible self-assembly properties as well as their suitability for both cargo loading and functionalization make them a versatile scaffold for numerous purposes. One of the main drawbacks of this platform is however its limited stability at physiological conditions. Herein, we report the development of a general reversible cross-linking strategy involving the homobifunctional cross-linker DTSSP (3,3'-dithiobis (sulfosuccinimidylpropionate)) which is suitable for particle stabilization. This methodology is adaptable to different CCMV variants in the presence or absence of a stabilizing cargo without varying neither particle shape nor size thus extending the potential use of these protein cages in nanomedical applications. Cross-linked particles are stable at neutral pH and 37 °C and they are capable of protecting loaded cargo against enzymatic digestion. Furthermore, the reversible nature of the cross-linking ensures particle disassembly when they are taken up by cells. This was demonstrated via the highly effective delivery of active siRNA into cells.

中文翻译:

多种可逆交联策略可稳定CCMV病毒样颗粒,从而有效地传递siRNA。

从the豆绿斑驳病毒(CCMV)获得的病毒样颗粒代表了药物输送应用的创新平台。它们独特的可逆自组装特性以及对货物装载和功能化的适用性,使其成为一种用途广泛的多功能支架。然而,该平台的主要缺点之一是其在生理条件下的有限的稳定性。本文中,我们报告了涉及同双功能交联剂DTSSP(3,3'-dithiobis(sulfosuccinimidylpropionate))的一般可逆交联策略的发展,该方法适用于颗粒稳定化。在存在或不存在稳定货物的情况下,该方法适用于不同的CCMV变体,而不会改变颗粒形状或大小,从而扩展了这些蛋白笼在纳米医学应用中的潜在用途。交联的颗粒在中性pH和37°C下稳定,并且能够保护装载的货物免受酶消化。此外,交联的可逆性质确保了当颗粒被细胞吸收时,颗粒会分解。这是通过将活性siRNA高效递送到细胞中来证明的。
更新日期:2019-12-06
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