PhaP介导EGFR靶向多肽修饰的肿瘤靶向PHBHHx纳米药物递送载体的构建

发布时间：2018-03-21 23:09

本文选题：PHA颗粒表面结合蛋白　切入点：-羟基丁酸--羟基己酸共聚酯　出处：《生物工程学报》2017年06期 　论文类型：期刊论文

【摘要】：聚羟基脂肪酸(PHA)颗粒表面结合蛋白Pha P具有与疏水性高分子材料表面紧密结合的能力,本研究将EGFR靶向多肽(ETP)与PhaP进行融合表达,构建了ETP-PhaP融合蛋白表达的重组工程菌Escherichia coli BL21(DE3)(pPI-ETP-P)。经对工程菌株的诱导表达及ETP-PhaP融合蛋白的纯化后,通过PhaP蛋白介导能够有效地将ETP-PhaP融合蛋白修饰于3-羟基丁酸-3-羟基己酸共聚酯(PHBHHx)纳米微球表面,构建成为具有EGFR靶向作用的药物递送载体。分别检测宫颈癌细胞系SiHa(EGFR高表达)和CaSKi(EGFR低表达)对ETP-PhaP修饰的PHBHHx纳米药物载体和未经修饰的纳米药物载体的吞噬情况。结果显示,纯化的ETP-PhaP融合蛋白能够很好地吸附于PHBHHx颗粒的表面,经ETP-PhaP融合蛋白修饰的PHBHHx纳米药物载体对EGFR高表达的宫颈癌Si Ha细胞的靶向效果强于EGFR低表达的CaSKi细胞系。这一结果表明了PhaP介导的PHBHHx纳米微球表面EGFR靶向多肽修饰具有简便、高效的优势,为疏水性纳米药物载体表面功能多肽修饰提供了一种新策略。
[Abstract]:The surface binding protein (Pha P) of polyhydroxyl fatty acid (PHA) particles has the ability to bind closely to the surface of hydrophobic polymer materials. In this study, EGFR targeting polypeptide (EGFR) and PhaP were fused and expressed. A recombinant engineering strain Escherichia coli BL21DE3 was constructed for the expression of ETP-PhaP fusion protein. The recombinant strain was induced to express and expressed ETP-PhaP fusion protein. The ETP-PhaP fusion protein can be effectively modified onto the surface of 3-hydroxybutyric acid-3-hydroxycaproic acid copolyester (PHBHHx) microspheres by PhaP protein mediated. EGFR targeting drug delivery vector was constructed. The high expression of SiHa(EGFR and low expression of CaSKi(EGFR were detected in cervical cancer cell line. The phagocytosis of ETP-PhaP modified PHBHHx nano-drug carrier and unmodified nano-drug carrier were detected. The results showed that, The purified ETP-PhaP fusion protein can be adsorbed on the surface of PHBHHx particles. The targeting effect of PHBHHx nanoparticles modified with ETP-PhaP fusion protein on SIHA cells with high expression of EGFR was stronger than that of CaSKi cells with low expression of EGFR. The results showed that PhaP mediated EGFR targeted polypeptide modification on PHBHHx nanoparticles was simple and convenient. The advantages of high efficiency provide a new strategy for surface modification of hydrophobic nano drug carriers.
【作者单位】：西安交通大学生命科学与技术学院生物医学信息工程教育部重点实验室;
【基金】：国家自然科学基金(Nos.81172170,81371288)资助~~
【分类号】：R73-36

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