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用于靶向卵巢癌基因治疗的功能化叶酸修饰氧化石墨烯/聚乙烯亚胺小干扰RNA纳米复合物

Functionalized Folate-Modified Graphene Oxide/PEI siRNA Nanocomplexes for Targeted Ovarian Cancer Gene Therapy.

作者信息

Wang Yunfei, Sun Guoping, Gong Yingying, Zhang Yuying, Liang Xiaofei, Yang Linqing

机构信息

Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, People's Republic of China.

Department of Pharmacy, Qingdao Seventh People's Hospital, 299 Nanjing Road, Qingdao, 266034, Shandong, People's Republic of China.

出版信息

Nanoscale Res Lett. 2020 Mar 6;15(1):57. doi: 10.1186/s11671-020-3281-7.

DOI:10.1186/s11671-020-3281-7
PMID:32140846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7058751/
Abstract

Gene therapy is emerging as a valid method for the treatment of ovarian cancer, including small interfering RNA (siRNA). Although it is so powerful, few targeting efficient gene delivery systems seriously hindered the development of gene therapy. In this study, we synthesized a novel gene vector PEG-GO-PEI-FA by functionalized graphene oxide (GO), in which folic acid (FA) can specifically bind to the folate receptor (FR), which is overexpressed in ovarian cancer. Characterizations of the nanocomplexes were evaluated by dynamic light scattering (DLS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The siRNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and lysosomal escape ability in ovarian cancer cells were investigated by confocal laser scanning microscopy. Furthermore, cellular biosafety of the system and inhibitory of the siRNA tolerability were evaluated by CCK-8 assay. The size of the PEG-GO-PEI-FA nanocomplexes was 216.1 ± 2.457 nm, exhibiting mild cytotoxicity in ovarian cancer cells. With high uptake efficiency, PEG-GO-PEI-FA can escape from the lysosome rapidly and release the gene. Moreover, PEG-GO-PEI-FA/siRNA can effectively inhibit the growth of ovarian cancer cells. By and large, the PEG-GO-PEI-FA/siRNA may offer a promising strategy for siRNA delivery in the treatment of FR-positive ovarian carcinoma or similar tumors.

摘要

基因治疗正在成为一种治疗卵巢癌的有效方法，包括小干扰RNA（siRNA）。尽管其作用强大，但极少有靶向高效的基因递送系统严重阻碍了基因治疗的发展。在本研究中，我们通过功能化氧化石墨烯（GO）合成了一种新型基因载体PEG-GO-PEI-FA，其中叶酸（FA）可特异性结合在卵巢癌中过表达的叶酸受体（FR）。通过动态光散射（DLS）、原子力显微镜（AFM）和傅里叶变换红外光谱（FTIR）对纳米复合物进行表征评估。通过琼脂糖凝胶电泳评估siRNA的凝聚能力和稳定性。通过共聚焦激光扫描显微镜研究卵巢癌细胞中的细胞摄取效率和溶酶体逃逸能力。此外，通过CCK-8测定评估该系统的细胞生物安全性和siRNA耐受性的抑制作用。PEG-GO-PEI-FA纳米复合物的大小为216.1±2.457nm，在卵巢癌细胞中表现出轻度细胞毒性。PEG-GO-PEI-FA具有高摄取效率，能够快速从溶酶体中逃逸并释放基因。此外，PEG-GO-PEI-FA/siRNA能够有效抑制卵巢癌细胞的生长。总体而言，PEG-GO-PEI-FA/siRNA可能为治疗FR阳性卵巢癌或类似肿瘤的siRNA递送提供一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/bf1bed72d11e/11671_2020_3281_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/260f02193551/11671_2020_3281_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/21b3f22cfd1c/11671_2020_3281_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/67bd84480f69/11671_2020_3281_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/f13c4fda2f0e/11671_2020_3281_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/b8f78589c1ce/11671_2020_3281_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/bf1bed72d11e/11671_2020_3281_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/260f02193551/11671_2020_3281_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/21b3f22cfd1c/11671_2020_3281_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/67bd84480f69/11671_2020_3281_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/f13c4fda2f0e/11671_2020_3281_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/b8f78589c1ce/11671_2020_3281_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/7058751/bf1bed72d11e/11671_2020_3281_Fig6_HTML.jpg

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