Journal of Controlled Release ( IF 10.5 ) Pub Date : 2021-01-07 , DOI: 10.1016/j.jconrel.2021.01.004
Bon Il Koo 1 , Inhye Kim 2 , Moon Young Yang 1 , Sung Duk Jo 1 , Kunmo Koo 1 , Seo Yeon Shin 3 , Kyung Mok Park 3 , Jong Min Yuk 1 , Eunji Lee 2 , Yoon Sung Nam 1
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Protein encapsulation into nanocarriers has been extensively studied to improve the efficacy and stability of therapeutic proteins. However, the chemical modification of proteins or new synthetic carrier materials are essential to achieve a high encapsulation efficiency and structural stability of proteins, which hinders their clinical applications. New strategies to physically incorporate proteins into nanocarriers feasible for clinical uses are required to overcome the current limitation. Here we report the spontaneous protein-induced reorganization of ‘pre-formed’ unilamellar lipid vesicles to efficiently incorporate proteins within multilamellar protein-lipid hybrid vesicles without chemical modification. Epidermal growth factor (EGF) binds to the surface of cationic unilamellar lipid vesicles and induces layer-by-layer self-assembly of the vesicles. The protein is spontaneously entrapped in the interstitial layers of a multilamellar structure with extremely high loading efficiency, ~99%, through polyionic interactions as predicted by molecular dynamics simulation. The loaded protein exhibits much higher structural, chemical, and biological stability compared to free protein. The method is also successfully applied to several other proteins. This work provides a promising method for the highly efficient encapsulation of therapeutic proteins into multilamellar lipid vesicles without the use of specialized instruments, high energy, coupling agents, or organic solvents.
中文翻译:
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蛋白质诱导的单层脂质囊泡向多层杂种囊泡变态
已经广泛研究了将蛋白质包封到纳米载体中以改善治疗性蛋白质的功效和稳定性。然而,蛋白质或新的合成载体材料的化学修饰对于实现蛋白质的高包封效率和结构稳定性是必不可少的,这阻碍了它们的临床应用。为了克服当前的局限性,需要新的策略将蛋白质物理掺入可用于临床的纳米载体中。在这里,我们报告自发的蛋白质诱导的'预先形成的'单层脂质囊泡的重组,以有效地将蛋白质掺入多层蛋白-脂质混合囊泡中,而无需化学修饰。表皮生长因子(EGF)与阳离子单层脂质囊泡的表面结合,并诱导囊泡的逐层自组装。通过分子动力学模拟预测的聚离子相互作用,蛋白质以极高的加载效率(〜99%)自发地捕获在多层结构的间隙层中。与游离蛋白相比,负载蛋白表现出更高的结构,化学和生物学稳定性。该方法还成功地应用于其他几种蛋白质。这项工作为将治疗性蛋白高效封装到多层脂质囊泡中提供了一种有前途的方法,而无需使用专门的仪器,高能,偶联剂或有机溶剂。通过分子动力学模拟预测的聚离子相互作用,蛋白质以极高的加载效率(〜99%)自发地捕获在多层结构的间隙层中。与游离蛋白相比,负载蛋白表现出更高的结构,化学和生物学稳定性。该方法还成功地应用于其他几种蛋白质。这项工作为将治疗性蛋白高效封装到多层脂质囊泡中提供了一种有前途的方法,而无需使用专门的仪器,高能,偶联剂或有机溶剂。通过分子动力学模拟预测的聚离子相互作用,蛋白质以极高的加载效率(〜99%)自发地捕获在多层结构的间隙层中。与游离蛋白相比,负载蛋白表现出更高的结构,化学和生物学稳定性。该方法还成功地应用于其他几种蛋白质。这项工作为将治疗性蛋白高效封装到多层脂质囊泡中提供了一种有前途的方法,而无需使用专门的仪器,高能,偶联剂或有机溶剂。和生物稳定性相比,游离蛋白。该方法还成功地应用于其他几种蛋白质。这项工作为将治疗性蛋白高效封装到多层脂质囊泡中提供了一种有前途的方法,而无需使用专门的仪器,高能,偶联剂或有机溶剂。和生物稳定性相比,游离蛋白。该方法还成功地应用于其他几种蛋白质。这项工作为将治疗性蛋白高效封装到多层脂质囊泡中提供了一种有前途的方法,而无需使用专门的仪器,高能,偶联剂或有机溶剂。