适配体C2min介导的可靶向2种前列腺癌基因的递送系统

张晶; 顾永卫; 武鑫

doi:10.3969/j.issn.1006-0111.201906038

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

x 关闭永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

适配体C2min介导的可靶向2种前列腺癌基因的递送系统

张晶, 顾永卫, 武鑫

文章导航 > 药学实践与服务 > 2020 > 38(1): 47-51,66

张晶, 顾永卫, 武鑫. 适配体C2min介导的可靶向2种前列腺癌基因的递送系统[J]. 药学实践与服务, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

引用本文:

张晶, 顾永卫, 武鑫. 适配体C2min介导的可靶向2种前列腺癌基因的递送系统[J]. 药学实践与服务, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

ZHANG Jing, GU Yongwei, WU Xin. The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

Citation:

ZHANG Jing, GU Yongwei, WU Xin. The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

适配体C2min介导的可靶向2种前列腺癌基因的递送系统

doi: 10.3969/j.issn.1006-0111.201906038

1.
内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050
2.
上海维洱实验室, 上海 201712
3.
内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050;上海维洱实验室, 上海 201712

基金项目: 国家自然科学基金（81072100）；上海市青年科技启明星计划资助（18QB1400400）

The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer

1.
Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
2.
Shanghai Wei Er Laboratory, shanghai 201712, China
3.
Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China;Shanghai Wei Er Laboratory, shanghai 201712, China

摘要: 目的通过合成可靶向两种前列腺癌的基因载体PAMAM-PEG-C2min，以提高基因的转染效率和肿瘤靶向性。方法将双功能聚乙二醇的一端与聚酰胺-胺（PAMAM）相连，另一端与适配体（C2min）连接，并利用¹H NMR技术对合成的PAMAM-PEG-C2min基因载体进行结构鉴定。通过两种前列腺癌PC3和LNCaP细胞的体外摄取和基因转染实验（包载siR-M基因），考察纳米复合物的生物学特性。并利用动物活体成像技术考察合成的纳米复合物的体内分布特征。结果核磁共振结果表明，本研究成功合成了PAMAM-PEG-C2min。PC3和LNCaP细胞对PAMAM-PEG-C2min的摄取结果体现出浓度依赖性。且与不经C2min修饰的PAMA-PEGM相比，PAMAM-PEG-C2min递药系统的基因转染效率和肿瘤细胞靶向性明显提高。体内靶向性结果表明，PAMAM-PEG-C2min可实现同时靶向2种前列腺癌组织的作用。结论本研究合成的PAMAM-PEG-C2min递送载体具有良好的肿瘤靶向性，为前列腺癌的综合治疗和靶向治疗提供了新的技术平台。
- 适配体 /
- 靶向 /
- 雄激素依赖型前列腺癌 /
- 雄激素非依赖型前列腺癌 /
- 基因载体
Abstract: Objective To synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min and improve gene transfection efficiency targeting on prostate cancer. Methods The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG). The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments (the loaded gene was siR-M) with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. The in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min were significantly improved compared with the PEG modified PAMAM. Conclusion PAMAM-PEG-C2min is a potential targeted drug delivery vehicle. It provides a new technology platform for comprehensive and specific targeting treatment of prostate cancer.
- adapter /
- targeting drug delivery /
- androgen-dependent prostate cancer /
- androgen-independent prostate cancer /
- gene vector

[1]	SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2019[J]. CA Cancer J Clin,2019,69(1):7-34
[2]	郑保良, 孙国庆. 激素敏感转移性前列腺癌的临床预后因素研究[J]. 实用癌症杂志, 2018, 33(6):995-997, 1017
[3]	DEN R B, GEORGE D, PIECZONKA C, et al. Ra-223 treatment for bone metastases in castrate-resistant prostate cancer: practical management issues for patient selection[J]. Am J Clin Oncol,2019,42(4):399-406
[4]	EL-AMM J, ARAGON-CHING J B. The changing landscape in the treatment of metastatic castration-resistant prostate cancer[J]. Ther Adv Med Oncol,2013,5(1):25-40
[5]	WU X, DING B Y, GAO J, et al. Second-generation aptamer-conjugated PSMA-targeted delivery system for prostate cancer therapy[J]. Int J Nanomedicine,2011,6:1747-1756
[6]	WILNER S E, WENGERTER B, MAIER K, et al. An RNA alternative to human transferrin: a new tool for targeting human cells[J]. Mol Ther Nucleic Acids,2012,1:e21
[7]	KELLY J M, AMOR-COARASA A, PONNALA S, et al. Albumin-binding PSMA ligands: implications for expanding the therapeutic window[J]. J Nucl Med,2019,60(5):656-663
[8]	HINSON D L, WEBBER R J. Miniaturization of the BCA protein assay[J]. BioTechniques,1988,6(1):14, 16, 19
[9]	NI X, CASTANARES M, MUKHERJEE A, et al. Nucleic acid aptamers: clinical applications and promising new horizons[J]. Curr Med Chem,2011,18(27):4206-4214
[10]	CHANG Y M, DONOVAN M J, TAN W H. Using aptamers for cancer biomarker discovery[J]. J Nucleic Acids,2013,2013:817350
[11]	CHUNG C H, KIM J H, JUNG J, et al. Nuclease-resistant DNA aptamer on gold nanoparticles for the simultaneous detection of Pb²⁺ and Hg²⁺ in human serum[J]. Biosens Bioelectron,2013,41:827-832
[12]	HUANG Y Z, HERNANDEZ F J, GU B, et al. RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB[J]. Mol Pharmacol,2012,82(4):623-635
[13]	SUNDARAM P, KURNIAWAN H, BYRNE M E, et al. Therapeutic RNA aptamers in clinical trials[J]. Eur J Pharm Sci,2013,48(1-2):259-271
[14]	PALMERSTON MENDES L, PAN J Y, TORCHILIN V P. Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy[J]. Molecules,2017,22(9):E1401
[15]	LU Y, JIANG W J, WU X, et al. Peptide T7-modified polypeptide with disulfide bonds for targeted delivery of plasmid DNA for gene therapy of prostate cancer[J]. Int J Nanomedicine,2018,13:6913-6927

[1]	李锐, 张倩倩, 王瑞冬, 高小峰. 国家集中带量采购政策下样本医院良性前列腺增生治疗药物使用情况分析 . 药学实践与服务, 2025, 43(2): 1-6. doi: 10.12206/j.issn.2097-2024.202408031
[2]	刘丽艳, 余小翠, 孙传铎. 纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044
[3]	杨嘉宁, 赵一颖, 肖伟. 七味脂肝方对非酒精性脂肪性肝炎动物模型的药效学评价 . 药学实践与服务, 2024, 42(9): 389-398. doi: 10.12206/j.issn.2097-2024.202404096
[4]	宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅. 帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
[5]	桂明珠, 李静, 李志玲. 儿童伏立康唑的血药浓度与CYP2C19、CYP2C9和CYP3A5基因多态性的相关性研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402020
[6]	黄韵, 张正银, 金英, 郑怡菁, 李铁军, 孙莉莉. 耐碳青霉烯类肺炎克雷伯菌及大肠埃希菌临床分离株耐药性及耐药基因分析 . 药学实践与服务, 2024, 42(10): 439-444. doi: 10.12206/j.issn.2097-2024.202309059
[7]	张广雨, 杜晶, 刘梦珍, 朱丹妮, 闫慧, 刘冲. 新斯的明与山莨菪碱联合应用对肺型氧中毒的保护作用及其机制的研究 . 药学实践与服务, 2024, 42(10): 433-438, 444. doi: 10.12206/j.issn.2097-2024.202310049
[8]	王雪莲, 郑斯莉, 李志勇, 罗亨宇, 缪朝玉. 全身过表达人METRNL基因小鼠模型的构建与验证 . 药学实践与服务, 2024, 42(5): 198-202, 222. doi: 10.12206/j.issn.2097-2024.202311014
[9]	毛智毅, 王筱燕, 陈晓颖, 汤逸斐. 度拉糖肽联合二甲双胍对肥胖型2型糖尿病患者机体代谢、体脂成分及血清脂肪因子的影响 . 药学实践与服务, 2024, 42(7): 305-309. doi: 10.12206/j.issn.2097-2024.202305032
[10]	冯志惠, 邓仪卿, 叶冰, 安培, 张宏, 张海军. 雀梅藤石油醚提取物诱导三阴性乳腺癌细胞凋亡的实验研究 . 药学实践与服务, 2024, 42(6): 253-259. doi: 10.12206/j.issn.2097-2024.202311055
[11]	姚瑞阳, 于海征, 李耀盺, 张磊. 丹参FBXL 基因家族的鉴定和表达模式分析 . 药学实践与服务, 2024, 42(11): 461-470. doi: 10.12206/j.issn.2097-2024.202407034
[12]	马兹芬, 许维恒, 金煜翔, 薛磊. 食管癌的靶向治疗与免疫治疗研究进展 . 药学实践与服务, 2024, 42(6): 231-237. doi: 10.12206/j.issn.2097-2024.202306008

点击查看大图

计量

文章访问数: 4667
HTML全文浏览量: 334
PDF下载量: 2786
被引次数: 0

适配体C2min介导的可靶向2种前列腺癌基因的递送系统

doi: 10.3969/j.issn.1006-0111.201906038

1. 内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050

2. 上海维洱实验室, 上海 201712

3. 内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050;上海维洱实验室, 上海 201712

基金项目: 国家自然科学基金（81072100）；上海市青年科技启明星计划资助（18QB1400400）

收稿日期: 2019-06-14
修回日期: 2019-07-26

关键词:

适配体 /

靶向 /

雄激素依赖型前列腺癌 /

雄激素非依赖型前列腺癌 /

基因载体

摘要: 目的通过合成可靶向两种前列腺癌的基因载体PAMAM-PEG-C2min，以提高基因的转染效率和肿瘤靶向性。方法将双功能聚乙二醇的一端与聚酰胺-胺（PAMAM）相连，另一端与适配体（C2min）连接，并利用¹H NMR技术对合成的PAMAM-PEG-C2min基因载体进行结构鉴定。通过两种前列腺癌PC3和LNCaP细胞的体外摄取和基因转染实验（包载siR-M基因），考察纳米复合物的生物学特性。并利用动物活体成像技术考察合成的纳米复合物的体内分布特征。结果核磁共振结果表明，本研究成功合成了PAMAM-PEG-C2min。PC3和LNCaP细胞对PAMAM-PEG-C2min的摄取结果体现出浓度依赖性。且与不经C2min修饰的PAMA-PEGM相比，PAMAM-PEG-C2min递药系统的基因转染效率和肿瘤细胞靶向性明显提高。体内靶向性结果表明，PAMAM-PEG-C2min可实现同时靶向2种前列腺癌组织的作用。结论本研究合成的PAMAM-PEG-C2min递送载体具有良好的肿瘤靶向性，为前列腺癌的综合治疗和靶向治疗提供了新的技术平台。

English Abstract

The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer

1. Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China

2. Shanghai Wei Er Laboratory, shanghai 201712, China

3. Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China;Shanghai Wei Er Laboratory, shanghai 201712, China

Received Date: 2019-06-14
Rev Recd Date: 2019-07-26

Keywords:

Abstract: Objective To synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min and improve gene transfection efficiency targeting on prostate cancer. Methods The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG). The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments (the loaded gene was siR-M) with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. The in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min were significantly improved compared with the PEG modified PAMAM. Conclusion PAMAM-PEG-C2min is a potential targeted drug delivery vehicle. It provides a new technology platform for comprehensive and specific targeting treatment of prostate cancer.

张晶, 顾永卫, 武鑫. 适配体C2min介导的可靶向2种前列腺癌基因的递送系统[J]. 药学实践与服务, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

引用本文:

张晶, 顾永卫, 武鑫. 适配体C2min介导的可靶向2种前列腺癌基因的递送系统[J]. 药学实践与服务, 2020, 38(1): 47-51,66. doi: 10.3969/j.issn.1006-0111.201906038

Citation:

全文HTML

参考文献 (15)

下载: 全尺寸图片幻灯片

返回文章

用微信扫码二维码

分享至好友和朋友圈

主管、主办: 中国人民解放军海军军医大学地址: 上海市杨浦区国和路325号邮政编码: 200433

电话: （021）81871324,81871397 E-mail: [email protected]

网站备案号沪ICP备05003363号-1

本系统由北京仁和汇智信息技术有限公司开发

留言板

适配体C2min介导的可靶向2种前列腺癌基因的递送系统

doi: 10.3969/j.issn.1006-0111.201906038

The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer

计量

出版历程

适配体C2min介导的可靶向2种前列腺癌基因的递送系统

doi: 10.3969/j.issn.1006-0111.201906038

1. 内蒙古医科大学附属医院药剂部, 内蒙古 呼和浩特 010050 2. 上海维洱实验室, 上海 201712 3. 内蒙古医科大学附属医院药剂部, 内蒙古 呼和浩特 010050;上海维洱实验室, 上海 201712

English Abstract

The C2min aptamer-modified gene delivery system for targeting ADPC/AIPC prostate cancer

全文HTML

目录

1. 内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050

2. 上海维洱实验室, 上海 201712

3. 内蒙古医科大学附属医院药剂部, 内蒙古呼和浩特 010050;上海维洱实验室, 上海 201712