Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging
Name
nihms895179.pdf
Description
Accepted version
Size
1.36 MB
Format
Unknown
Checksum (MD5)
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Author(s)
Fay, Francois
Hansen, Line
Hectors, Stefanie JCG
Sanchez-Gaytan, Brenda L
Zhao, Yiming
Tang, Jun
Munitz, Jazz
Alaarg, Amr
Braza, Mounia S
Gianella, Anita
Date Issued
2017
Journal
Bioconjugate Chemistry
Publisher
American Chemical Society (ACS)
Version
Author's final manuscript
Abstract
© 2017 American Chemical Society. Active targeting of nanoparticles through surface functionalization is a common strategy to enhance tumor delivery specificity. However, active targeting strategies tend to work against long polyethylene glycol's shielding effectiveness and associated favorable pharmacokinetics. To overcome these limitations, we developed a matrix metalloproteinase-2 sensitive surface-converting polyethylene glycol coating. This coating prevents nanoparticle-cell interaction in the bloodstream, but, once exposed to matrix metalloproteinase-2, i.e., when the nanoparticles accumulate within the tumor interstitium, the converting polyethylene glycol coating is cleaved, and targeting ligands become available for binding to tumor cells. In this study, we applied a comprehensive multimodal imaging strategy involving optical, nuclear, and magnetic resonance imaging methods to evaluate this coating approach in a breast tumor mouse model. The data obtained revealed that this surface-converting coating enhances the nanoparticle's blood half-life and tumor accumulation and ultimately results in improved tumor-cell targeting. Our results show that this enzyme-specific surface-converting coating ensures a high cell-targeting specificity without compromising favorable nanoparticle pharmacokinetics.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/ACS.BIOCONJCHEM.7B00086
