Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging.
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.
Francois
0000-0001-7405-5600
F
Fay
Interdisciplinary Nanoscience Center (iNANO), Aarhus University , Aarhus DK-8000, Denmark.
Line
L
Hansen
Stefanie J C G
SJCG
Hectors
Brenda L
BL
Sanchez-Gaytan
Yiming
0000-0003-1660-0679
Y
Zhao
Department of Radiology, Memorial Sloan-Kettering Cancer Center , New York City, New York 10065, United States.
Jun
0000-0002-8285-5111
J
Tang
Jazz
J
Munitz
Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede 7522 NB, The Netherlands.
Amr
A
Alaarg
Mounia S
MS
Braza
Anita
A
Gianella
Stuart A
SA
Aaronson
Department of Radiology, Memorial Sloan-Kettering Cancer Center , New York City, New York 10065, United States.
Thomas
T
Reiner
Interdisciplinary Nanoscience Center (iNANO), Aarhus University , Aarhus DK-8000, Denmark.
Jørgen
J
Kjems
Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
Robert
0000-0003-4255-0492
R
Langer
SyMO-Chem B.V. , Eindhoven 5612 AZ, The Netherlands.
Freek J M
FJM
Hoeben
SyMO-Chem B.V. , Eindhoven 5612 AZ, The Netherlands.
Henk M
HM
Janssen
Claudia
C
Calcagno
Gustav J
GJ
Strijkers
Zahi A
ZA
Fayad
Carlos
C
Pérez-Medina
Willem J M
WJM
Mulder
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D013055:Spectrophotometry, Infrared / Q000379:methods*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2