Multimodal QDot Based Nanoprobe for RealTime Noninvasive Bioimaging

1
Multimodal QDot Based Nanoprobe for Real-Time
Noninvasive Bioimaging NIRT -0506560
Brij M. Moudgil1, Edward W. Scott 2, Glenn A.
Walter3, Swadeshmukul Santra4 1Department of
Materials Science and Engineering Particle
Engineering Research Center, 2Department of
Molecular Genetics and Microbiology, 3Department
of Physiology and Functional Genomics, University
of Florida 4NanoScience Technology Center,
Department of Chemistry and Biomolecular Science
Center, University of Central Florida.

Beacon Proposed (ß- gal) and Alternative (Halo
Tag)
Synthesis and Characterization of NIR Qdot Core

• Proposed Beacon Galactopyranose (Gal) and QDot
  are conjugated to modified Cyclen and Gd
  (III)

• Developed CdSMn/SiO2 and CdSMn/SiO2/Gd
  Multimodal Qdots

Micro emulsion route Water dispersible 20nm
590 emission In vitro, in vivo studies
Limitation Visible emission
Differentiation
EgadMe based design synthesized and
characterized

• Synthesized CdTexSe(1-x) Qdots

Hot phase (Trioctylphosphine) route 600-850
emission 70 Quantum Yield (QY)
Limitation Enzyme activation did not generate
enhanced MR contrast Possible reasons Steric
factor(s) mutarotation of ß galactose
irreproducibility of EgadMe (NMR in
BioMedicine,2007,20, 275-290)
Limitation Significant decrease in QY on ligand
exchange/coating

• Synthesized CdTexS(1-x) Qdots

( Modified literature protocol )
Hydrothermal route 500-750 emission 40 QY
Water dispersible

• Alternate approach Halo TagTM ( engineered
  genes)

• Halo Tag -fused to surface receptor - expressed
  under tissue specific promoter
• Upon differentiation cell specific HaloTag
  expression will be targeted using MQdots

(c) Western Blot ladder (Lane 1), C2C12 (2),
C2C12 transfected with the HaloTag (3), HEK-293
(4) and 293 transfected with HaloTag plasmid (
5).
spectra
C2C12 cells transfected by electroporation
with pDisplay-Halo Tag plasmid (a) bright
field and (b) labeled with TMR-HaloTag ligand.
spectra
Halo Tag transduction capacity checked on
HEK-293 and C2C12 cells
Developed water dispersible, bright, Visible-NIR
emitting Qdots
Timeline
Synthesis of Multimodal Quantum Dots (MQDots)
Bimodal in vivo imaging of bone marrow cell homing

Objective Track in vivo translocation of labeled
bone marrow (BM) cells
(MQDots)
(H2O)

(d)
(a)
(b)
(c)
(d)
MQDots (a) Schematic (b) TEM 20nm (c) bright
yellow emission (d) labeled stem cells (muscle)
Large (cf. Gd-DOTA) R1 and R2 relaxivity values
of MQDots (4.7T)
Manuscript under preparation
(A) Ex-vivo and (B) in-vivo MRI of labeled stem
cells in mouse pup brain
Manuscript under preparation

• Fluorescent labeling allows real time optical
  tracking of stem cells
• Ultra-high field MRI allows detection of small
  numbers of labeled cells .

Bright and photostable CdSMn/ ZnS/SiO2-Gd Qdots
developed ( Advanced Material 2006, 18,
2890)
AcknowledgementNSF-NIRT Grant EEC 0506560