Cell membrane adhesive n-hexadecyl choline phosphate as vaccine delivery systems for anticancer immunotherapy

Cell membrane adhesive n-hexadecyl choline phosphate as vaccine delivery systems for anticancer immunotherapy
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细胞膜粘合剂正十六烷基磷酸胆碱作为抗癌免疫治疗的疫苗递送系统

DOI:
10.1016/j.cej.2018.11.227
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发表时间:
2019-03
影响因子:
15.1
通讯作者:
Liu Zonghua
Liu Zonghua
中科院分区:
工程技术1区
文献类型:
--
作者:
Li Sha;Qu Yangchun;Yu Xifei;Xue Wei;Liu Zonghua

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近年来,肿瘤免疫治疗作为新一代肿瘤治疗策略,显示出巨大的潜力,受到越来越多的关注。然而,肿瘤相关抗原如果单独使用不能诱导有效的免疫应答。因此,有效的肿瘤治疗需要疫苗递送系统的辅助,以引发强烈的抗肿瘤免疫应答。本研究合成了一种新型的细胞膜粘附疫苗载体--正十六烷基磷酸胆碱(C16-CP),并对该载体的模型抗原卵清蛋白(OVA)的递送和抗肿瘤治疗进行了评价。磷酸胆碱(CP)基团与细胞膜组分二棕榈酰磷脂酰胆碱的磷脂酰胆碱基团方向相反,因此具有静电吸引力。此外,利用正十六烷基链对CP基团进行疏水修饰,制备了一种细胞膜粘附分子C16-CP,该分子通过静电吸引和疏水作用粘附于细胞膜上。CP基团在中性pH环境下带正电荷。因此,阳离子脂质C16-CP可以通过静电吸引和疏水相互作用与OVA相互作用。在这项工作中,C16-CP协助抗原递送的潜力进行了评估,以开发一种新的疫苗递送系统。
In recent years, cancer immunotherapy as a new generation of cancer treatment strategy has displayed promising potential and attracted more and more attention. However, tumor-associated antigens if used alone could not induce potent immune responses. Therefore, efficient tumor treatment demands the assistance of vaccine delivery systems to elicit strong anti-tumor immune responses. In this study, a novel cell membrane adhesive vaccine carrier—n-hexadecyl choline phosphate (C16-CP) was synthesized and evaluated for the delivery of model antigen ovalbumin (OVA) and for anticancer therapy. Choline phosphate (CP) group is orientated opposite to and hence has electrostatic attraction with the phosphatidylcholine group of cell membrane component dipalmitoyl phosphatidylcholine. Moreover, CP group was hydrophobically modified withn-hexadecyl chain to prepare a cell membrane adhesive molecule C16-CP, which could adhere to cell membrane through electrostatic attraction and hydrophobic interaction. The CP group is positively charged at neutral pH environment. Hence, the cationic lipid C16-CP could interact with OVA through electrostatic attraction and hydrophobic interaction. In this work, the potential of C16-CP to assist antigen delivery was evaluated in order to develop a novel vaccine delivery system.
基于多价磷酸胆碱的生物可还原聚合物纳米载体,用于增强阿霉素的细胞摄取和细胞内递送
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