Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 5, Issue 1, Pages 73-82Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2008.07.007
Keywords
Peptides; Tumor targeting; Tumor vessels; Drug delivery; Tumor markers
Funding
- NCI NIH HHS [R01 CA115410-01, CA19335, R01 CA115410, P01 CA104898-01A20002, CA104898, CA124427, CA115410, P01 CA104898, U54 CA119335-010001, R01 CA124427-02, R01 CA124427, U54 CA119335] Funding Source: Medline
- NHLBI NIH HHS [U01 HL080718, U01 HL080718-01, HL080718] Funding Source: Medline
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We have used tumor-homing peptides to target abraxane, a clinically approved paclitaxel-albumin nanoparticle, to tumors in mice. The targeting was accomplished with two peptides, CREKA and LyP-1 (CGNKRTRGC). Fluorescein (FAM)-labeled CREKA-abraxane, when injected intravenously into mice bearing MDA-MB-435 human cancer xenografts, accumulated in tumor blood vessels, forming aggregates that contained red blood cells and fibrin. FAM-LyP-1-abraxane co-localized with extravascular islands expressing its receptor, p32. Self-assembled mixed micelles carrying the homing peptide and the label on different subunits accumulated in the same areas of tumors as LyP-1-abraxane, showing that Lyp-1 can deliver intact nanoparticles into extravascular sites. Untargeted, FAM-abraxane was detected in the form of a faint meshwork in tumor interstitium. LyP-1-abraxane produced a statistically highly significant inhibition of tumor growth compared with untargeted abraxane. These results show that nanoparticles can be effectively targeted into extravascular tumor tissue and that targeting can enhance the activity of a therapeutic nanoparticle. (C) 2009 Elsevier Inc. All rights reserved.
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