Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels

被引：115

作者：

Hallahan, D ^{[4
]}

Geng, L

Qu, SM

Scarfone, C

Giorgio, T

Donnelly, E

Gao, X

Clanton, J

机构：

[1] Vanderbilt Univ, Dept Radiol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Radiat Oncol, Nashville, TN 37232 USA

[5] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

来源：

CANCER CELL | 2003年 / 3卷 / 01期

关键词：

D O I：

10.1016/S1535-6108(02)00238-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The objective of this study was to target drug delivery to radiation-induced neoantigens, which include activated receptors within the tumor vasculature. These responses include posttranslational changes in pre-existing proteins, which can be discovered by phage-displayed peptide libraries administered to mice bearing irradiated tumors. Phage-displayed peptides recovered from irradiated tumors included the amino acid sequence RGDGSSV. This peptide binds to integrins within the tumor microvasculature. Immunohistochemical staining of irradiated tumors showed accumulation of fibrinogen receptor alpha(2b)beta(3) integrin. We studied tumor targeting efficiency of ligands to radiation-induced alpha(2b)beta(3). Radiopharmaceuticals were localized to irradiated tumors by use of alpha(2b)beta(3) ligands conjugated to nanoparticles and liposomes. Fibrinogen-conjugated nanoparticles bind to the radiation-activated receptor, obliterate tumor blood flow, and significantly increase regression and growth delay in irradiated tumors. Radiation-guided drug delivery to tumor blood vessels is a novel paradigm for targeted drug delivery.

引用

页码：63 / 74

页数：12

共 50 条

[1] 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

[2] TUMOR VASCULATURE - A POTENTIAL THERAPEUTIC TARGET [J].

BAILLIE, CT ;

WINSLET, MC ;

BRADLEY, NJ .

BRITISH JOURNAL OF CANCER, 1995, 72 (02) :257-267

[3] Radiopharmaceuticals to image infection and inflammation [J].

Boerman, OC ;

Rennen, H ;

Oyen, WJG ;

Corstens, FHM .

SEMINARS IN NUCLEAR MEDICINE, 2001, 31 (04) :286-295

[4] INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS [J].

BROOKS, PC ;

MONTGOMERY, AMP ;

ROSENFELD, M ;

REISFELD, RA ;

HU, TH ;

KLIER, G ;

CHERESH, DA .

CELL, 1994, 79 (07) :1157-1164

[5]

Burg MA, 1999, CANCER RES, V59, P2869

[6] FRAMESHIFTING IN GENE-10 OF BACTERIOPHAGE-T7 [J].

CONDRON, BG ;

ATKINS, JF ;

GESTELAND, RF .

JOURNAL OF BACTERIOLOGY, 1991, 173 (21) :6998-7003

[7] Quantified power Doppler US of tumor blood flow correlates with microscopic quantification of tumor blood vessels [J].

Donnelly, EF ;

Geng, L ;

Wojcicki, WE ;

Fleischer, AC ;

Hallahan, DE .

RADIOLOGY, 2001, 219 (01) :166-170

[8]

DVORAK HF, 1991, CANCER CELL-MON REV, V3, P77

[9] Anti-cancer activity of targeted pro-apoptotic peptides [J].

Ellerby, HM ;

Arap, W ;

Ellerby, LM ;

Kain, R ;

Andrusiak, R ;

Del Rio, G ;

Krajewski, S ;

Lombardo, CR ;

Rao, R ;

Ruoslahti, E ;

Bredesen, DE ;

Pasqualini, R .

NATURE MEDICINE, 1999, 5 (09) :1032-1038

[10] Seminars in medicine of the Beth Israel Hospital, Boston - Clinical applications of research on angiogenesis [J].

Folkman, J .

NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (26) :1757-1763

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