3 years ago

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

Investigating the Cellular Specificity in Tumors of a Surface-Converting Nanoparticle by Multimodal Imaging
Jørgen Kjems, Thomas Reiner, Jazz Munitz, Francois Fay, Line Hansen, Stefanie J. C. G. Hectors, Freek J. M. Hoeben, Jun Tang, Gustav J. Strijkers, Brenda L. Sanchez-Gaytan, Yiming Zhao, Mounia S. Braza, Carlos Pérez-Medina, Robert Langer, Stuart A. Aaronson, Zahi A. Fayad, Anita Gianella, Amr Alaarg, Claudia Calcagno, Henk M. Janssen, Willem J.M. Mulder
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.

Publisher URL: http://dx.doi.org/10.1021/acs.bioconjchem.7b00086

DOI: 10.1021/acs.bioconjchem.7b00086

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