TY - JOUR
T1 - Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging
AU - Fay, Francois
AU - Hansen, Line
AU - Hectors, Stefanie J. C. G.
AU - Sanchez-Gaytan, Brenda L.
AU - Zhao, Yiming
AU - Tang, Jun
AU - Munitz, Jazz
AU - Alaarg, Amr
AU - Braza, Mounia S.
AU - Gianella, Anita
AU - Aaronson, Stuart A.
AU - Reiner, Thomas
AU - Kjems, Jurgen
AU - Langer, Robert
AU - Hoeben, Freek J. M.
AU - Janssen, Henk M.
AU - Calcagno, Claudia
AU - Strijkers, Gustav J.
AU - Fayad, Zahi A.
AU - Perez-Medina, Carlos
AU - Mulder, Willem J. M.
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.1021/acs.bioconjchem.7b00086
DO - https://doi.org/10.1021/acs.bioconjchem.7b00086
M3 - Article
C2 - 28316241
SN - 1043-1802
VL - 28
SP - 1413
EP - 1421
JO - Bioconjugate chemistry
JF - Bioconjugate chemistry
IS - 5
ER -