Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Francois Fay, Icahn School of Medicine at Mount Sinai
  • ,
  • Line Hansen, Icahn School of Medicine at Mount Sinai
  • ,
  • Stefanie J. C. G. Hectors, Icahn School of Medicine at Mount Sinai
  • ,
  • Brenda L. Sanchez-Gaytan, Icahn School of Medicine at Mount Sinai
  • ,
  • Yiming Zhao, Icahn School of Medicine at Mount Sinai
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  • Bao-Jun Tang, Memorial Sloan Kettering Cancer Center, Icahn School of Medicine at Mount Sinai
  • ,
  • Jazz Munitz, Icahn School of Medicine at Mount Sinai
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  • Amr Alaarg, Twente University, Icahn School of Medicine at Mount Sinai
  • ,
  • Mounia S. Braza, Icahn School of Medicine at Mount Sinai
  • ,
  • Anita Gianella, Icahn School of Medicine at Mount Sinai
  • ,
  • Stuart A. Aaronson, Icahn School of Medicine at Mount Sinai
  • ,
  • Thomas Reiner, Memorial Sloan Kettering Cancer Center
  • ,
  • Jørgen Kjems
  • Robert Langer, Massachusetts Institute of Technology, MIT, Cambridge,
  • Freek J. M. Hoeben, SyMO Chem BV
  • ,
  • Henk M. Janssen, SyMO Chem BV
  • ,
  • Claudia Calcagno, Icahn School of Medicine at Mount Sinai
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  • Gustav J Strijkers, Icahn School of Medicine at Mount Sinai, Academic Medical Center, University of Amsterdam, Amsterdam
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  • Zahi A Fayad, Icahn School of Medicine at Mount Sinai
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  • Carlos Perez-Medina, Icahn School of Medicine at Mount Sinai
  • ,
  • Willem J M Mulder, Icahn School of Medicine at Mount Sinai

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
JournalBioconjugate Chemistry
Volume28
Issue5
Pages (from-to)1413-1421
Number of pages9
ISSN1043-1802
DOIs
Publication statusPublished - 2017

    Research areas

  • DRUG-DELIVERY, IN-VIVO, MACROMOLECULAR THERAPEUTICS, CANCER-TREATMENT, GENE DELIVERY, RGD, VASCULATURE, ACCUMULATION, FLUORESCENCE, ENDOTHELIUM

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