RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

被引:432
作者
Temming, K
Schiffelers, RM
Molema, G
Kok, RJ
机构
[1] Univ Groningen, Inst Drug Explorat, Dept Pharmacokinet & Drug Delivery, NL-9713 AV Groningen, Netherlands
[2] KREATECH Biotechnol BV, Amsterdam, Netherlands
[3] Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Utrecht, Netherlands
[4] Univ Groningen, Univ Med Ctr Groningen, Med Biol Sect, Dept Pathol & Lab Med, NL-9700 AB Groningen, Netherlands
关键词
Arg-Gly-Asp; RGD; endothelial cells; angiogenesis; antivascular therapies; cancer; drug delivery; gene delivery; therapeutic proteins; polymers; cytostatic drugs; radiotracer;
D O I
10.1016/j.drup.2005.10.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization Of alpha(v)beta(3)-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alpha(v)beta(3). We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed. (C) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:381 / 402
页数:22
相关论文
共 162 条
[1]   Adenovirus type 41 lacks an RGD αv-integrin binding motif on the penton base and undergoes delayed uptake in A549 cells [J].
Albinsson, B ;
Kidd, AH .
VIRUS RESEARCH, 1999, 64 (02) :125-136
[2]  
Anderson SA, 2000, MAGNET RESON MED, V44, P433, DOI 10.1002/1522-2594(200009)44:3<433::AID-MRM14>3.0.CO
[3]  
2-9
[4]   Peptidomimetics - Antagonists of the fibrinogen receptors: Molecular design, structures, properties and therapeutic applications [J].
Andronati, SA ;
Karaseva, TL ;
Krysko, AA .
CURRENT MEDICINAL CHEMISTRY, 2004, 11 (09) :1183-1211
[5]  
[Anonymous], LETT DRUG DES DISCOV
[6]   Peptide-mediated gene transfer of cationic lipid/plasmid DNA complexes to endothelial cells [J].
Anwer, K ;
Kao, G ;
Rolland, A ;
Driessen, WHP ;
Sullivan, SM .
JOURNAL OF DRUG TARGETING, 2004, 12 (04) :215-221
[7]   RNA interference may be more potent than antisense RNA in human cancer cell lines [J].
Aoki, Y ;
Cioca, DP ;
Oidaira, H ;
Kamiya, J ;
Kiyosawa, K .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2003, 30 (1-2) :96-102
[8]   Potential tumor-targeting peptide vector of histidylated oligolysine conjugated to a tumor-homing RGD motif [J].
Aoki, Y ;
Hosaka, S ;
Kawa, S ;
Kiyosawa, K .
CANCER GENE THERAPY, 2001, 8 (10) :783-787
[9]   Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model [J].
Arap, W ;
Pasqualini, R ;
Ruoslahti, E .
SCIENCE, 1998, 279 (5349) :377-380
[10]   Molecular organization of protein-DNA complexes for cell-targeted DNA delivery [J].
Arís, A ;
Villaverde, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 278 (02) :455-461