Internally Cationic Polyamidoamine PAMAM-OH Dendrimers for siRNA Delivery: Effect of the Degree of Quaternization and Cancer Targeting

被引：174

作者：

Patil, Mahesh L. ^{[1
]}

Zhang, Min ^{[1
]}

Taratula, Oleh ^{[2
]}

Garbuzenko, Olga B. ^{[1
]}

He, Huixin ^{[2
]}

Minko, Tamara ^{[1
]}

机构：

[1] Rutgers State Univ, Dept Pharmaceut, Piscataway, NJ 08854 USA

[2] Rutgers State Univ, Dept Chem, Newark, NJ 07102 USA

来源：

BIOMACROMOLECULES | 2009年 / 10卷 / 02期

关键词：

GENE DELIVERY; INTRACELLULAR DELIVERY; RNA INTERFERENCE; DRUG; EXPRESSION; EFFICIENT; SYSTEMS; TOXICOGENOMICS; ANTISENSE; PEPTIDES;

D O I：

10.1021/bm8009973

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel cancer targeted, internally cationic and surface neutral polyamidoamine (PAMAM) dendrimer, was designed, synthesized, and evaluated as a nanocarrier for the targeted intracellular delivery of siRNA. The dendrimer contained a synthetic analog of Luteinizing hormone-releasing hormone as cancer targeting moiety. The proposed delivery system possesses the following advantages: (1) internal cationic charges for complexation with siRNA and enhanced siRNA protection; (2) low cytotoxicity; (3) lesser degree of quaternization offering free tertiary amines for potential proton sponge effect; and (4) targeting specifically to cancer cells for enhancing siRNA uptake and efficiency and potential limitation of adverse side effects of chemotherapy on healthy organs. Both nontargeted and targeted dendrimer-siRNA complexes formed compact nanometer size spherical particles, exhibited very low cytotoxicity even at the higher concentration, and efficiently penetrated cancer cells in vitro. However, only the targeted dendrimer-siRNA complex was able to substantially decrease the expression of a targeted BCL2 gene.

引用

页码：258 / 266

页数：9

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