Single-Step Assembly of Multimodal Imaging Nanocarriers: MRI and Long-Wavelength Fluorescence Imaging

Nathalie M. Pinkerton, Marian E. Gindy, Victoria L. Calero-Ddelc, Theodore Wolfson, Robert F. Pagels, Derek Adler, Dayuan Gao, Shike Li, Ruobing Wang, Margot Zevon, Nan Yao, Carlos Pacheco, Michael J. Therien, Carlos Rinaldi, Patrick J. Sinko, Robert K. Prud'homme

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Magnetic resonance imaging (MRI)- and near-infrared (NIR)-active, multimodal composite nanocarriers (CNCs) are prepared using a simple one-step process, flash nanoprecipitation (FNP). The FNP process allows for the independent control of the hydrodynamic diameter, co-core excipient and NIR dye loading, and iron oxide-based nanocrystal (IONC) content of the CNCs. In the controlled precipitation process, 10 nm IONCs are encapsulated into poly(ethylene glycol) (PEG) stabilized CNCs to make biocompatible T2 contrast agents. By adjusting the formulation, CNC size is tuned between 80 and 360 nm. Holding the CNC size constant at an intensity weighted average diameter of 99 ± 3 nm (PDI width 28 nm), the particle relaxivity varies linearly with encapsulated IONC content ranging from 66 to 533 × 10-3m-1 s-1 for CNCs formulated with 4-16 wt% IONC. To demonstrate the use of CNCs as in vivo MRI contrast agents, CNCs are surface functionalized with liver-targeting hydroxyl groups. The CNCs enable the detection of 0.8 mm3 non-small cell lung cancer metastases in mice livers via MRI. Incorporating the hydrophobic, NIR dye tris-(porphyrinato)zinc(II) into CNCs enables complementary visualization with long-wavelength fluorescence at 800 nm. In vivo imaging demonstrates the ability of CNCs to act both as MRI and fluorescent imaging agents.

Original languageEnglish (US)
Pages (from-to)1376-1385
Number of pages10
JournalAdvanced Healthcare Materials
Volume4
Issue number9
DOIs
StatePublished - Jun 1 2015

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Keywords

  • Composite nanocarrier
  • Flash nanoprecipitation
  • MRI contrast agents
  • Metastasis detection
  • Multimodal imaging

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  • Cite this

    Pinkerton, N. M., Gindy, M. E., Calero-Ddelc, V. L., Wolfson, T., Pagels, R. F., Adler, D., Gao, D., Li, S., Wang, R., Zevon, M., Yao, N., Pacheco, C., Therien, M. J., Rinaldi, C., Sinko, P. J., & Prud'homme, R. K. (2015). Single-Step Assembly of Multimodal Imaging Nanocarriers: MRI and Long-Wavelength Fluorescence Imaging. Advanced Healthcare Materials, 4(9), 1376-1385. https://doi.org/10.1002/adhm.201400766