Single-Step Assembly of Multimodal Imaging Nanocarriers: MRI and Long-Wavelength Fluorescence Imaging.
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(-3) m(-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 mm(3) 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.
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Nathalie M
NM
Pinkerton
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Marian E
ME
Gindy
Department of Chemical Engineering, University of Puerto Rico, Mayagüez, 00681, Puerto Rico.
Victoria L
VL
Calero-DdelC
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Theodore
T
Wolfson
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Robert F
RF
Pagels
College of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.
Derek
D
Adler
College of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.
Dayuan
D
Gao
College of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.
Shike
S
Li
Department of Chemistry, Duke University, Durham, NC, 27708, USA.
Ruobing
R
Wang
Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, 08854, USA.
Margot
M
Zevon
Princeton Materials Institute, Princeton University, Princeton, NJ, 08540, USA.
Nan
N
Yao
Department of Chemistry, University of Connecticut, Storrs, CT, 06269, USA.
Carlos
C
Pacheco
Department of Chemistry, Duke University, Durham, NC, 27708, USA.
Michael J
MJ
Therien
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, 32605, USA.
Carlos
C
Rinaldi
College of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.
Patrick J
PJ
Sinko
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, 08544, USA.
Robert K
RK
Prud'homme
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
D003287:Contrast Media; D004337:Drug Carriers; D005290:Ferric Compounds; D005456:Fluorescent Dyes; C000499:ferric oxide; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000
MRI contrast agents; composite nanocarrier; flash nanoprecipitation; metastasis detection; multimodal imaging