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

Article

Fay, F., Hansen, L., Hectors, S.J.C.G., Sanchez-Gaytan, B.L., Zhao, Y., Tang, J., Munitz, J., Alaarg, A., Braza, M.S., Gianella, A., Aaronson, S.A., Reiner, T., Kjems, J., Langer, R., Hoeben, F.J.M., Janssen, H.M., Calcagno, C., Strijkers, G.J., Fayad, Z.A., Pérez-Medina, C. & Mulder, W.J.M. (2017). Investigating the cellular specificity in tumors of a surface-converting nanoparticle by multimodal imaging. Bioconjugate Chemistry, 28(5), 1413-1421. In Scopus Cited 0 times.

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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.