Targeting of albumin-embedded paclitaxel nanoparticles to tumors

Karmali, Priya Prakash; Kotamraju, Venkata Ramana; Kastantin, Mark; Black, Matthew; Missirlis, Dimitris; Tirrell, Matthew; Ruoslahti, Erkki

doi:10.1016/j.nano.2008.07.007

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 1 , Pages 73-82, March 2009

Targeting of albumin-embedded paclitaxel nanoparticles to tumors

Priya Prakash Karmali, PhD
- Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California, USA
- Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California, USA
Venkata Ramana Kotamraju, PhD
- Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California, USA
- Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California, USA
Mark Kastantin, SB
- Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, California, USA
Matthew Black, BS
- Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, California, USA
Dimitris Missirlis, PhD
- Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, California, USA
Matthew Tirrell, PhD
- Department of Chemical Engineering and Materials Research Laboratory, University of California, Santa Barbara, California, USA
Erkki Ruoslahti, MD, PhD
- Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California, USA
- Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California, USA
- Corresponding author. Burnham Institute for Medical Research at UCSB, University of California, Santa Barbara, California 93106-9610, USA.

Received 19 June 2008; accepted 30 July 2008. published online 02 October 2008.

Abstract

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.

Key words: Peptides, Tumor targeting, Tumor vessels, Drug delivery, Tumor markers

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This work was supported by National Cancer Institute grants CA119335, CA124427, CA115410, CA104898, and, in part, National Heart, Lung and Blood Institute grant HL080718 and MRSEC Program of the National Science Foundation under Award DMR05-20415.

PII: S1549-9634(08)00124-X

doi:10.1016/j.nano.2008.07.007

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 1 , Pages 73-82, March 2009

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