Investigating the cellular specificity in tumors of a surface-converting nanoparticle by multimodal imaging

F. Fay, L. Hansen, S.J.C.G. Hectors, B.L. Sanchez-Gaytan, Y. Zhao, J. Tang, J. Munitz, A. Alaarg, M.S. Braza, A. Gianella, S.A. Aaronson, T. Reiner, J. Kjems, R. Langer, F.J.M. Hoeben, H.M. Janssen, C. Calcagno, G.J. Strijkers, Z.A. Fayad, C. Pérez-MedinaW.J.M. Mulder

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1413-1421
Number of pages9
JournalBioconjugate Chemistry
Volume28
Issue number5
DOIs
Publication statusPublished - 17 May 2017

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