Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers

Kezheng Wang, Dipanjan Pan, Anne H. Schmieder, Angana Senpan, Dennis E. Hourcade, Christine T.N. Pham, Lynne M. Mitchell, Shelton D. Caruthers, Grace Cui, Samuel A. Wickline, Baozhong Shen, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138 ± 10 (Dav)/nm; PDI: 0.06; zeta: -27 ± 2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk.

Original languageEnglish
Pages (from-to)601-609
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Complement activation
  • Contrast media
  • Gadolinium
  • MRI
  • Manganese
  • Nanoparticle

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