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Theranostic Layer‐by‐Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing
Name
nihms-1066484.pdf
Description
Accepted version
Size
1.96 MB
Format
Adobe PDF
Checksum (MD5)
8c27a5ef4523dfa508857e36d5adab48
Author(s) • • • • • •
Boehnke, Natalie
Correa, Santiago
Hao, Liangliang
Wang, Wade
Straehla, Joelle P
Bhatia, Sangeeta N
Hammond, Paula T
Date Issued
2020
Journal
Angewandte Chemie - International Edition
Publisher
Wiley
Version
Author's final manuscript
Abstract
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Layer-by-layer nanoparticles (NPs) are modular drug delivery vehicles that incorporate multiple functional materials through sequential deposition of polyelectrolytes onto charged nanoparticle cores. Herein, we combined the multicomponent features and tumor targeting capabilities of layer-by-layer assembly with functional biosensing peptides to create a new class of nanotheranostics. These NPs encapsulate a high weight percentage of siRNA while also carrying a synthetic biosensing peptide on the surface that is cleaved into a urinary reporter upon exposure to specific proteases overexpressed in the tumor microenvironment. Importantly, this biosensor reports back on a molecular signature characteristic to metastatic tumors and associated with poor prognosis, MMP9 protease overexpression. This nanotheranostic mediates noninvasive urinary-based diagnostics in mouse models of three different cancers with simultaneous gene silencing in flank and metastatic mouse models of ovarian cancer.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1002/ANIE.201911762