Reversal of multidrug resistance by reduction-sensitive linear cationic click polymer/iMDR1-pDNA complex nanoparticles

被引：51

作者：

Gao, Yu ^{[1
]}

Chen, Lingli ^{[1
]}

Zhang, Zhiwen ^{[1
]}

Chen, Yi ^{[1
]}

Li, Yaping ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China

来源：

BIOMATERIALS | 2011年 / 32卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Click chemistry; RNA interference; Disulfide bond; P-glycoprotein; Multidrug resistance; BIOREDUCIBLE POLY(AMIDO AMINE)S; BREAST-CANCER; GENE DELIVERY; IN-VIVO; POLYMERS; STRATEGIES; LIGATION; AGENTS; AZIDES;

D O I：

10.1016/j.biomaterials.2010.11.001

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

A reduction-sensitive linear cationic click polymer (RCP) was specially designed for the efficient gene delivery to overcome multidrug resistance (MDR) by RNA interference to silence the expression of P-glycoprotein (P-gp). RCP was synthesized via the "click chemistry" with disulfide bonds, amide triazole moieties and secondary amine groups in the main chain. RCP could efficiently condense pDNA into nanoparticles (RCPNs) around 150 nm. Polyplex dissociation was observed in the presence of 2.5 mm DTT due to the cleavage of disulfide bonds, which indicated the efficient DNA release under the reduction condition. In vitro transfection and cytotoxicity experiments against human breast cancer MCF-7 cells and drug-resistant MCF-7/ADR cells showed that RCPNs could bring about higher transfection efficiency with much lower cytotoxicity than PEI/DNA nanoparticles. RCPNs loaded with plasmid iMDR1-pDNA could inhibit P-gp expression, increase adriamycin (ADR) accumulation and enhance cytotoxicity of ADR against MCF-7/ADR cells. Combination of RCPNs and ADR could suppress the tumor growth more efficiently than using ADR only on mouse xenograft model bearing ADR resistant human breast cancer. These results suggested that this RCP could be a potential, safe and efficient non-viral vector for reversing MDR. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1738 / 1747

页数：10

共 42 条

[1] In vitro and in vivo study of an albumin-binding prodrug of doxorubicin that is cleaved by cathepsin B [J].

Abu Ajaj, Khalid ;

Graeser, Ralph ;

Fichtner, Iduna ;

Kratz, Felix .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2009, 64 (02) :413-418

[2] Development of strategies for conditional RNA interference [J].

Allen, Danny ;

Kenna, Paul F. ;

Palfi, Arpad ;

McMahon, Helena P. ;

Millington-Ward, Sophia ;

O'Reilly, Mary ;

Humphries, Peter ;

Farrar, G. Jane .

JOURNAL OF GENE MEDICINE, 2007, 9 (04) :287-298

[3] Association and dissociation characteristics of polymer/DNA complexes used for gene delivery [J].

Arigita, C ;

Zuidam, NJ ;

Crommelin, DJA ;

Hennink, WE .

PHARMACEUTICAL RESEARCH, 1999, 16 (10) :1534-1541

[4]

BERTRAND C, 1993, J ORG CHEM, V58, P3736

[5]

Bugano DDG, 2008, EUR J GYNAECOL ONCOL, V29, P313

[6] Multidrug resistance/P-glycoprotein and breast cancer: Review and meta-analysis [J].

Clarke, R ;

Leonessa, F ;

Trock, B .

SEMINARS IN ONCOLOGY, 2005, 32 (06) :S9-S15

[7] Click chemistry in materials synthesis.: 1.: Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition [J].

Díaz, DD ;

Punna, S ;

Holzer, P ;

Mcpherson, AK ;

Sharpless, KB ;

Fokin, VV ;

Finn, MG .

JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2004, 42 (17) :4392-4403

[8]

Faneyte IF, 2001, INT J CANCER, V93, P114, DOI 10.1002/1097-0215(20010701)93:1<114::AID-IJC1309>3.3.CO

[9]

2-A

[10] Allosteric inhibition of protein-DNA complexes by polyamide-intercalator conjugates [J].

Fechter, EJ ;

Dervan, PB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (28) :8476-8485

← 1 2 3 4 5 →