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智能 TAT 偶联抗 HER2 免疫脂质体敲低 MDR1 产生多药耐药癌的化疗增敏表型。

Intelligent TAT-coupled anti-HER2 immunoliposomes knock downed MDR1 to produce chemosensitize phenotype of multidrug resistant carcinoma.

机构信息

Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

J Cell Physiol. 2019 Nov;234(11):20769-20778. doi: 10.1002/jcp.28683. Epub 2019 Apr 18.

DOI:10.1002/jcp.28683
PMID:31001890
Abstract

Gene therapy using biocompatible cationic liposomes is amongst promising approaches that decreases death from cancers. Here an invasive multidrug resistant cell model has been developed by lentiviral transfection. In parallel phospholipids have been covalently conjugated to TAT, MMP2, and Herceptin. The functional lipids have been mixed to generate intelligent liposome harboring small interfering RNA (siRNA) with high efficiency. The final liposomal complex was uniformly monodisperse and particle dimension and zeta-potential were respectively around 200 nm and -42.21 mV. Minimal cytotoxic effects have been reported for nanocarriers due to good biocompatibility of the selected phospholipids. Flourescence-activated cell sorter (FACS) analyses have been represented that surface trastuzumab and TAT specifically promote cellular uptake of liposomes in the malignant tumor cells. Assessment of MDR1 transcript and protein expression has been exhibited maximum significant downregulation around of 128-fold and 50-fold, respectively after 48 hr of liposome exposure. As it has been concluded, targeted liposomes may become a potential tool in gene delivery for improving chemotherapeutic efficiency in cancer treatment.

摘要

利用生物相容性阳离子脂质体进行基因治疗是一种很有前途的方法,可以降低癌症死亡率。在这里,通过慢病毒转染开发了一种侵袭性多药耐药细胞模型。同时,将磷脂共价连接到 TAT、MMP2 和赫赛汀上。将功能脂质混合以生成高效携带小干扰 RNA(siRNA)的智能脂质体。最终的脂质体复合物均匀单分散,粒径和 Zeta 电位分别约为 200nm 和-42.21mV。由于所选磷脂的良好生物相容性,纳米载体的细胞毒性最小。荧光激活细胞分选(FACS)分析表明,表面曲妥珠单抗和 TAT 特异性促进了恶性肿瘤细胞对脂质体的摄取。脂质体暴露 48 小时后,MDR1 转录本和蛋白表达的评估显示,最大下调倍数分别约为 128 倍和 50 倍。综上所述,靶向脂质体可能成为基因传递的一种潜在工具,以提高癌症治疗中的化疗效率。

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