Experimental Study on the Synthesis of Organism Carrier Disulfide Cross-linked Polyethylenimines and Its Delivering Ability for Small Interfering RNA_West China Medical Journal

Authors：

ZHANG Yuna ¹ ,  XIA Wei ² , NI Jing ² , WANG Guoyu ¹ , ZHUANG Juhua ²

Department of Nuclear Medicine, Shanghai Putuo District People‘s Hospital, Shanghai 200060, P. R. China;

Corresponding?author：

XIA Wei, Email: zyn3091181@sina.com

Keywords：

載體; 聚乙烯亞胺; 合成; 小干擾RNA; 遞送

DOI：

10.7507/1002-0179.20130001

Video：

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目的　合成可生物降解的基因載體，并分析其生物毒性及轉染率。方法　低分子量聚乙烯亞胺（PEI）通過雙硫鍵交聯合成可降解的高分子量PEI衍生物（SS-PEI），通過紅外光譜和核磁波譜分析技術分析其化學結構，采用細胞活力實驗和檢測大鼠肝腎功能指標分析其細胞和體內毒性，并轉染羥基熒光素修飾的siRNA（FAM-siRNA）分析細胞轉染率。結果　紅外波譜和核磁波譜分析可見酰胺鍵的特征波譜，噻唑藍法和肝腎功能指標顯示SS-PEI不同劑量組與對照組的差異均無統計學意義（P＞0.05），SS-PEI/FAM-siRNA轉染率為（76.0 ± 2.8）%。結論　SS-PEI的合成可明顯提高裝載siRNA的效率，具有安全、高效等特點。

Citation： ZHANG Yuna,XIA Wei,NI Jing,WANG Guoyu,ZHUANG Juhua. Experimental Study on the Synthesis of Organism Carrier Disulfide Cross-linked Polyethylenimines and Its Delivering Ability for Small Interfering RNA. West China Medical Journal, 2013, 28(1): 1-5. doi: 10.7507/1002-0179.20130001 Copy

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5.	Li SD, Huang L. Nonviral is superior to viral gene delivery[J]. J Control Release, 2007, 123(3): 181-183.
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11.	Li J, Piao YF, Jiang Z, et al. Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice[J]. World J Gastroenterol, 2009, 15(21): 2602-2608.
12.	Huang C, Jiang T, Zhu L, et al. STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo[J]. Int J Oncol, 2011, 38(6): 1637-1644.
13.	De Souza Nascimento P, Alves G, Fiedler W. Telomerase inhibition by an siRNA directed against hTERT leads to telomere attrition in HT29 cells[J]. Oncol Rep, 2006, 16(2): 423-428.
14.	Lin C, Engbersen JF. The role of the disulfide group in disulfide-based polymeric gene carriers[J]. Expert Opin Drug Deliv, 2009, 6(4): 421-439.
15.	Liu J, Jiang X, Xu L, et al. Novel reduction-responsive cross-linked polyethylenimine derivatives by click chemistry for nonviral gene delivery[J]. Bioconjug Chem, 2010, 21(10): 1827-1835.
16.	Choi S, Lee KD. Enhanced gene delivery using disulfide-crosslinked low molecular weight polyethylenimine with listeriolysin o-polyethylenimine disulfide conjugate[J]. J Control Release, 2008, 131(1): 70-76.
17.	Breunig M, Lungwitz U, Liebl R, et al. Breaking up the correlation between efficacy and toxicity for nonviral gene delivery[J]. Proc Natl Acad Sci U S A, 2007, 104(36): 14454-14459.
18.	Lin C, Blaauboer CJ, Timoneda MM, et al. Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery[J]. J Control Release, 2008, 126(2): 166-174.
19.	Piest M, Lin C, Mateos-Timoneda MA, et al. Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: structure effects and in vitro gene transfer properties[J]. J Control Release, 2008, 130(1): 38-45.
20.	Piest M, Engbersen JF. Role of boronic acid moieties in poly(amido amine)s for gene delivery[J]. J Control Release, 2011, 155(2): 331-340.

1. 　Wenqi D, Li W, Shanshan C, et al. EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer[J]. J Cancer Res Clin Oncol, 2009, 135(9): 1277-1285.
2. 　Zhou H, Tang Y, Liang X, et al. RNAi targeting urokinase-type plasminogen activator receptor inhibits metastasis and progression of oral squamous cell carcinoma in vivo[J]. Int J Cancer, 2009, 125(2): 453-462.
3. 　Kanwar JR, Kamalapuram SK, Kanwar RK. Targeting survivin in cancer: patent review[J]. Expert Opin Ther Pat, 2010, 20(12): 1723-1737.
4. 　Chen T, Deng C. Inhibitory effect of siRNA targeting survivin in gastric cancer MGC-803 cells[J]. Int Immunopharmacol, 2008, 8(7): 1006-1011.
5. 　Li SD, Huang L. Nonviral is superior to viral gene delivery[J]. J Control Release, 2007, 123(3): 181-183.
6. 　王青松, 方曉玲. 非病毒載體在腫瘤基因治療領域的研究進展[J]. 藥物生物技術, 2005, 12(2): 125-129.
7. 　Lungwitz UT. Polyethylenimine-based non-viral gene delivery systems[J]. Eur J Pharm Biopharm, 2005, 60(2): 247-266.
8. 　Han S, Mahato RI, Sung YK, et al. Development of biomaterials for gene therapy[J]. Mol Ther, 2000, 2(4): 302-317.
9. 　Fornari F, Gramantieri L, Ferracin M, et al. MiR-221 con-trols CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma[J]. Oncogene, 2008, 27(43): 5651-5661.
10. 　Gandellini P, Folini M, Bandiera R, et al. Down-regulation of human telomerase reverse transcriptase through specific activation of RNAi pathway quickly results in cancer cell growth impairment[J]. Biochem Pharmacol, 2007, 73(11): 1703-1714.
11. 　Li J, Piao YF, Jiang Z, et al. Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice[J]. World J Gastroenterol, 2009, 15(21): 2602-2608.
12. 　Huang C, Jiang T, Zhu L, et al. STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo[J]. Int J Oncol, 2011, 38(6): 1637-1644.
13. 　De Souza Nascimento P, Alves G, Fiedler W. Telomerase inhibition by an siRNA directed against hTERT leads to telomere attrition in HT29 cells[J]. Oncol Rep, 2006, 16(2): 423-428.
14. 　Lin C, Engbersen JF. The role of the disulfide group in disulfide-based polymeric gene carriers[J]. Expert Opin Drug Deliv, 2009, 6(4): 421-439.
15. 　Liu J, Jiang X, Xu L, et al. Novel reduction-responsive cross-linked polyethylenimine derivatives by click chemistry for nonviral gene delivery[J]. Bioconjug Chem, 2010, 21(10): 1827-1835.
16. 　Choi S, Lee KD. Enhanced gene delivery using disulfide-crosslinked low molecular weight polyethylenimine with listeriolysin o-polyethylenimine disulfide conjugate[J]. J Control Release, 2008, 131(1): 70-76.
17. 　Breunig M, Lungwitz U, Liebl R, et al. Breaking up the correlation between efficacy and toxicity for nonviral gene delivery[J]. Proc Natl Acad Sci U S A, 2007, 104(36): 14454-14459.
18. 　Lin C, Blaauboer CJ, Timoneda MM, et al. Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery[J]. J Control Release, 2008, 126(2): 166-174.
19. 　Piest M, Lin C, Mateos-Timoneda MA, et al. Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: structure effects and in vitro gene transfer properties[J]. J Control Release, 2008, 130(1): 38-45.
20. 　Piest M, Engbersen JF. Role of boronic acid moieties in poly(amido amine)s for gene delivery[J]. J Control Release, 2011, 155(2): 331-340.

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Experimental Study on the Synthesis of Organism Carrier Disulfide Cross-linked Polyethylenimines and Its Delivering Ability for Small Interfering RNA

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