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A computational framework for identifying design guidelines to increase the penetration of targeted nanoparticles into tumors

Paper ID Volume ID Publish Year Pages File Format Full-Text
32103 44900 2013 11 PDF Available
Title
A computational framework for identifying design guidelines to increase the penetration of targeted nanoparticles into tumors
Abstract

•Binding and diffusion affect the penetration of targeted nanoparticles in tumors.•Simulations show many nanoparticle formulations accumulate in cells near vessels.•Shielding prevents nanoparticles from binding until they diffuse deep in tissue.•Shielding strategy is generalizable to many nanoparticles and tumor scenarios.•Time or space-dependent binding enables engineered nanoparticle tissue distributions.

SummaryTargeted nanoparticles are increasingly being engineered for the treatment of cancer. By design, they can passively accumulate in tumors, selectively bind to targets in their environment, and deliver localized treatments. However, the penetration of targeted nanoparticles deep into tissue can be hindered by their slow diffusion and a high binding affinity. As a result, they often localize to areas around the vessels from which they extravasate, never reaching the deep-seeded tumor cells, thereby limiting their efficacy. To increase tissue penetration and cellular accumulation, we propose generalizable guidelines for nanoparticle design and validate them using two different computer models that capture the potency, motion, binding kinetics, and cellular internalization of targeted nanoparticles in a section of tumor tissue. One strategy that emerged from the models was delaying nanoparticle binding until after the nanoparticles have had time to diffuse deep into the tissue. Results show that nanoparticles that are designed according to these guidelines do not require fine-tuning of their kinetics or size and can be administered in lower doses than classical targeted nanoparticles for a desired tissue penetration in a large variety of tumor scenarios. In the future, similar models could serve as a testbed to explore engineered tissue-distributions that arise when large numbers of nanoparticles interact in a tumor environment.

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Keywords
Targeting; Nanoparticle; Modeling; Tissue penetration; Cancer; Systems nanotechnology
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A computational framework for identifying design guidelines to increase the penetration of targeted nanoparticles into tumors
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 8, Issue 6, December 2013, Pages 566–576
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