LHRH Receptor-Mediated Delivery of siRNA Using Polyelectrolyte Complex Micelles Self-Assembled from siRNA-PEG-LHRH Conjugate and PEI

被引：90
作者：
Kim, Sun Hwa [1 ,2 ]
Jeong, Ji Hoon [3 ]
Lee, Soo Hyeon [1 ]
Kim, Sung Wan [2 ]
Park, Tae Gwan [1 ]
机构：
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[2] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Ctr Controlled Chem Delivery, Salt Lake City, UT 84112 USA
[3] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea
来源：
BIOCONJUGATE CHEMISTRY | 2008年 / 19卷 / 11期
关键词：
D O I：
10.1021/bc800249n
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Polyelectrolyte complex (PEC) micelles modified with cancer cell targeting moieties were prepared for intracellular delivery of vascular endothelial growth factor (VEGF) small interfering RNA (siRNA). A luteinizing hormone-releasing hormone (LHRH) peptide analogue was coupled as a cancer targeting ligand to the distal end of the poly(ethylene glycol) (PEG)-siRNA conjugate. The siRNA-PEG-LHRH conjugate self-assembled to form nanosized PEC micelles upon mixing with poly(ethylenimine) (PEI) via ionic interactions. The PEC micelles showed spherical morphology with a hydrodynamic diameter of ca. 150 nm. For LHRH receptor overexpressing ovarian cancer cells (A2780), the PEC micelles with LHRH exhibited enhanced cellular uptake compared to those without LHRH, resulting in increased VEGF gene silencing efficiency via receptor-mediated endocytosis. This study showed that PEC micelles decorated with specific cell-recognizable targeting ligands could be used for targeted delivery of siRNA.
引用
收藏
页码：2156 / 2162
页数：7
相关论文
共 24 条
  • [1] Gene therapy targeting to tumor endothelium
    Bazan-Peregrino, M.
    Seymour, L. W.
    Harris, A. L.
    [J]. CANCER GENE THERAPY, 2007, 14 (02) : 117 - 127
  • [2] Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide
    Dharap, SS
    Wang, Y
    Chandna, P
    Khandare, JJ
    Qiu, B
    Gunaseelan, S
    Sinko, PJ
    Stein, S
    Farmanfarmaian, A
    Minko, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (36) : 12962 - 12967
  • [3] Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides
    Dharap, SS
    Qiu, B
    Williams, GC
    Sinko, P
    Stein, S
    Minko, T
    [J]. JOURNAL OF CONTROLLED RELEASE, 2003, 91 (1-2) : 61 - 73
  • [4] Targeted proapoptotic LHRH-BH3 peptide
    Dharap, SS
    Minko, T
    [J]. PHARMACEUTICAL RESEARCH, 2003, 20 (06) : 889 - 896
  • [5] Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
    Elbashir, SM
    Harborth, J
    Lendeckel, W
    Yalcin, A
    Weber, K
    Tuschl, T
    [J]. NATURE, 2001, 411 (6836) : 494 - 498
  • [6] Delivering RNA interference to the mammalian brain
    Fountaine, TM
    Wood, MJA
    Wade-Martins, R
    [J]. CURRENT GENE THERAPY, 2005, 5 (04) : 399 - 410
  • [7] Effects on RNA interference in gene expression (RNAi) in cultured mammalian cells of mismatches and the introduction of chemical modifications at the 3′-ends of siRNAs
    Hamada, M
    Ohtsuka, T
    Kawaida, R
    Koizumi, M
    Morita, K
    Furukawa, H
    Imanishi, T
    Miyagishi, M
    Taira, K
    [J]. ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 2002, 12 (05): : 301 - 309
  • [8] Post-transcriptional gene silencing by double-stranded RNA
    Hammond, SM
    Caudy, AA
    Hannon, GJ
    [J]. NATURE REVIEWS GENETICS, 2001, 2 (02) : 110 - 119
  • [9] Comparative studies of suppression of malignant cancer cell phenotype by antisense oligo DNA and small interfering RNA
    Hiroi, N
    Funahashi, A
    Kitano, H
    [J]. CANCER GENE THERAPY, 2006, 13 (01) : 7 - 12
  • [10] Ligand-targeted delivery of therapeutic siRNA
    Ikeda, Yutaka
    Taira, Kazunari
    [J]. PHARMACEUTICAL RESEARCH, 2006, 23 (08) : 1631 - 1640
123