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用于肺癌靶向基因治疗的叶酸偶联多胺

Folate-conjugated polyspermine for lung cancer-targeted gene therapy.

作者信息

Zhang Mei, Kim You-Kyoung, Cui Pengfei, Zhang Jialiang, Qiao Jianbin, He Yujing, Lyu Jinyuan, Luo Chengqiong, Xing Lei, Jiang Hulin

机构信息

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.

出版信息

Acta Pharm Sin B. 2016 Jul;6(4):336-43. doi: 10.1016/j.apsb.2016.03.010. Epub 2016 Apr 12.

DOI:10.1016/j.apsb.2016.03.010
PMID:27471674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4951589/
Abstract

Biodegradable polyamines have long been studied as potential recombinant viral gene vectors. Spermine (SPE) is an endogenous tetra-amine with excellent biocompatibility yet poor gene condensation capacity. We have previously synthesized a polyspermine based on SPE and poly(ethylene glycol) (PEG) diacrylate (SPE-alt-PEG) for enhanced transfection performance, but the synthesized SPE-alt-PEG still lacked specificity towards cancer cells. In this study, folic acid (FA) was incorporated into SPE-alt-PEG to fabricate a targeted gene delivery vector (FA-SPE-PEG) via an acylation reaction. FA-SPE-PEG exhibited mild cytotoxicity in both cancer cells and normal cells. FA-SPE-PEG possessed higher transfection efficiency than PEI 25 K and Lipofectamine(®) 2000 in two tested cancer cell lines at functional weight ratios, and its superiority over untargeted SPE-alt-PEG was prominent in cells with overexpressed folate receptors (FRs). Moreover, in vivo delivery of green fluorescent protein (GFP) with FA-SPE-PEG resulted in highest fluorescent signal intensity of all investigated groups. FA-SPE-PEG showed remarkably enhanced specificity towards cancer cells both in vivo and in vitro due to the interaction between FA and FRs. Taken together, FA-SPE-PEG was demonstrated to be a prospective targeted gene delivery vector with high transfection capacity and excellent biocompatibility.

摘要

可生物降解的多胺长期以来一直作为潜在的重组病毒基因载体进行研究。精胺（SPE）是一种内源性四胺，具有优异的生物相容性，但基因凝聚能力较差。我们之前基于SPE和聚乙二醇（PEG）二丙烯酸酯合成了一种聚精胺（SPE-alt-PEG）以提高转染性能，但合成的SPE-alt-PEG对癌细胞仍缺乏特异性。在本研究中，通过酰化反应将叶酸（FA）掺入SPE-alt-PEG中以制备靶向基因递送载体（FA-SPE-PEG）。FA-SPE-PEG在癌细胞和正常细胞中均表现出轻微的细胞毒性。在功能重量比下，FA-SPE-PEG在两种测试的癌细胞系中比PEI 25K和Lipofectamine® 2000具有更高的转染效率，并且在叶酸受体（FRs）过表达的细胞中，其相对于非靶向的SPE-alt-PEG的优势尤为突出。此外，用FA-SPE-PEG进行绿色荧光蛋白（GFP）的体内递送在所有研究组中产生了最高的荧光信号强度。由于FA与FRs之间的相互作用，FA-SPE-PEG在体内和体外均显示出对癌细胞的特异性显著增强。综上所述，FA-SPE-PEG被证明是一种具有高转染能力和优异生物相容性的前瞻性靶向基因递送载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/f38f4a867742/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/544229e2ae8f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/1fc95f9d1577/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/19085d338168/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/c910e5282dff/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/1ce92b725fbe/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/f38f4a867742/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/544229e2ae8f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/1fc95f9d1577/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/19085d338168/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/c910e5282dff/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/1ce92b725fbe/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfd2/4951589/f38f4a867742/gr5.jpg

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