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Drug-induced amplification of nanoparticle targeting to tumors

Paper ID Volume ID Publish Year Pages File Format Full-Text
32161 44906 2014 10 PDF Available
Title
Drug-induced amplification of nanoparticle targeting to tumors
Abstract

•Vascular-disrupting agent, ombrabulin, increases tumor presentation of p32 protein.•Ombrabulin pre-treatment increases tumor accumulation of p32-binding nanoparticles.•Amplified delivery of therapeutic nanoparticles improves treatment of tumors.

Nanomedicines have the potential to significantly impact cancer therapy by improving drug efficacy and decreasing off-target effects, yet our ability to efficiently home nanoparticles to disease sites remains limited. One frequently overlooked constraint of current active targeting schemes is the relative dearth of targetable antigens within tumors, which restricts the amount of cargo that can be delivered in a tumor-specific manner. To address this limitation, we exploit tumor-specific responses to drugs to construct a cooperative targeting system where a small molecule therapeutic modulates the disease microenvironment to amplify nanoparticle recruitment in vivo. We first administer a vascular disrupting agent, ombrabulin, which selectively affects tumors and leads to locally elevated presentation of the stress-related protein, p32. This increase in p32 levels provides more binding sites for circulating p32-targeted nanoparticles, enhancing their delivery of diagnostic or therapeutic cargos to tumors. We show that this cooperative targeting system recruits over five times higher doses of nanoparticles to tumors and decreases tumor burden when compared with non-cooperative controls. These results suggest that using nanomedicine in conjunction with drugs that enhance the presentation of target antigens in the tumor environment may be an effective strategy for improving the diagnosis and treatment of cancer.

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Keywords
Nanomedicine; Active targeting; Cancer therapy; Vascular disrupting agent; Liposomes; Magnetic nanoworms
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Drug-induced amplification of nanoparticle targeting to tumors
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 9, Issue 5, October 2014, Pages 550–559
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us