Robust Polyion Complex Vesicles (PICsomes) under Physiological Conditions Reinforced by Multiple Hydrogen Bond Formation Derived by Guanidinium Groups
Robust Polyion Complex Vesicles (PICsomes) under Physiological Conditions Reinforced by Multiple Hydrogen Bond Formation Derived by Guanidinium Groups
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DOI：
10.1021/acs.biomac.8b01097
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发表时间：
2018-10-01
影响因子：
6.2
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Hori, Mao;Cabral, Horacio;Kataoka, Kazunori
由带相反电荷的块状和均聚电解质对自组装形成的聚离子复合囊泡（PICsome）在生物活性剂的功能负载方面显示出卓越的特征。然而，PICsomes的稳定性在生理环境中经常受到损害，并且只有具有化学交联膜的PICsomes才能在恶劣的体内条件下（例如在血流中）经受住考验。在此，我们开发了多功能的 PICsome，旨在通过离子键和氢键的组合（广泛存在于天然蛋白质中作为盐桥）稳定其膜，通过在聚阳离子部分中控制引入胍基以实现同时的聚离子络合和氢键，从而在体内环境中持续存在。胍基化的PICsomes在生理盐条件下成功组装，通过调整胍含量以及阴离子和阳离子组分的比例来精确控制其形态。与纳米载体开发相关的直径为100 nm的胍基化PICsomes在高尿素浓度、生理温度和血清孵育下稳定，在体内血液循环中持续存在。
Polyion complex vesicles (PICsomes) formed from a self-assembly of an oppositely charged pair of block- and homo-polyelectrolytes have shown exceptional features for functional loading of bioactive agents. Nevertheless, the stability of PICsomes is often jeopardized in a physiological environment, and only PICsomes having chemically cross-linked membranes have endured in harsh in vivo conditions, such as in the bloodstream. Herein, we developed versatile PICsomes aimed to last in in vivo settings by stabilizing their membrane through a combination of ionic and hydrogen bonding, which is widely found in natural proteins as a salt bridge, by controlled introduction of guanidinium groups in the polycation fraction toward concurrent polyion complexation and hydrogen bonding. The guanidinylated PICsomes were successfully assembled under physiological salt conditions, with precise control of their morphology by tuning the guanidinium content, and the ratio of anionic and cationic components. Guanidinylated PICsomes with 100 nm diameter, which are relevant to nanocarrier development, were stable in high urea concentration, at physiological temperature, and under serum incubation, persisting in blood circulation in vivo.