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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
Adobe PDF
Checksum (MD5)
6552e3ee0ae8faa5feeb874c2e504e1b
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.
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DOI of Published Version
10.1021/ACS.BIOCONJCHEM.7B00086
