Selective agents for sensing and imaging
based on functional DNA nanotechnology
Yi Lu
Department of Chemistry, Biochemistry, Bioengineering,
Materials Science and Engineering,
Center for Biophysics and Computational Biology, and
Beckman Institute for Advanced Science and Technology
University of Illinois at Urbana-Champaign
Urbana, IL 61801
There are a number of imaging technologies
http://www.beckman.illinois.edu/intim/index.aspx
Fluorescence, x-ray computed tomography (CT), magnetic resonance imaging (MRI),
ultrasound imaging, Optical Coherence Tomography (OCT), and nuclear imaging with positron
emission tomography (PET) and single-photon emission computed tomography (SPECT).
Can we increase the contrast between the target(s) and the surrounding?
There are a number of novel materials as contrast agents
Fluorophores/florescent proteins
Nanotubes
Nanoparticles
Nanorings
Quantum dots
Nanowires
DNA functionalized gold nanoparticles
as imaging agents
Most DNA-nanomaterials are prepared after nanomaterials are synthesized
Dwight S. Seferos, David A. Giljohann, Haley D. Hill, Andrew E. Prigodich, and Chad A. Mirkin,
J. Am. Chem. Soc., 2007, 129 (50), pp 15477–15479).
DNA sequence-dependent shape control of AuNP
During AuNP synthesis
Zidong Wang, Jieqian Zhang, Jonathan M. Ekman, Paul
J. A. Kenis and Yi Lu, Nano Lett. 10, 1886–1891 (2010).
Stability of the DNA on the AuNF
Poly A
Poly C
Poly T
No DNA
Overnight incubation with 14 mM mercaptoethanol removed 100%DNA from thio-AuNS
Overnight incubation with 14 mM mercaptoethanol removed ~30% DNA from AuNF
Zidong Wang, Jieqian Zhang, Jonathan M. Ekman, Paul J. A. Kenis and Yi Lu, Nano Lett. 10, 1886–1891 (2010).
Cellular uptake and imaging
AuNF treated cells
Control with AuNS
AuNFs got into cells after incubation with cells
AuNFs can be readily imaged under dark field light scattering imaging
Minimal cyto-toxicity was observed.
Potential applications in intercellular imaging and gene or drug delivery.
Zidong Wang, Jieqian Zhang, Jonathan M. Ekman, Paul J. A. Kenis and Yi Lu, Nano Lett. 10, 1886–1891 (2010).
A gap between imaging technologies and
biology/medical sciences: selective imaging
• Can we detect molecular markers for tumor before tumor develops?
• Every biologist and medical doctor has their own favorite targets; can the
imaging technique be applied to see those specific targets?
• Until recently, antibodies have been used to provide selective imaging;
However, antibodies are large size, high costs and low stability
and are not effective against:
small molecular targets
targets too toxic to raise antibodies
conditions not optimal for antibody functions.\
sometimes too big for dynamic imaging
An even bigger gap between imaging technologies and
biomedical sciences: selective imaging of small molecules
Sarcosine: Small prostate cancer
PSA: Large prostate cancer marker
marker discovered
currently used
~90% correlation
61-78% false positive rate
15-27% false negative rate
(Clin. Chem. 2001, 47:1472) (Nature, 2009, 457:910)
Well developed: large molecular markers such as DNA, RNA and proteins
Less well developed: small molecular markers:
Metabolites:
metal ions: calcium, iron….
organic molecules: ATP, NADH, hormone, receptor….
(biomarkers for healthy human being)
Invasive species: metal ions: lead, mercury…
organic molecules: dioxins, pesticides, melamine, sarcosine.
(biomarkers for diseases such as cancer)
A number of non-DNA/RNA/Protein biomarkers remain to be discovered and detected
Correlation of metabolites/biomarkers with DNA/RNA/Protein levels and with biological function
is an unmet challenge in molecular imaging.
Four key steps in designing imaging agents
for a broad range of targets
? a general method to obtain molecules for any specific
target (e.g., Pb2+, Amphetamine, cocaine, Ricin, cancer)
?
a general method to improve selectivity;
a general method to transform molecular
recognition into physical detectable signals without
compromising the binding affinity and selectivity;
?
a general method to fine-tune the dynamic range to
match those of interests
?
Four key steps in designing imaging agents
? a general method to obtain molecules for any specific
target (e.g., Pb2+, Amphetamine, cocaine, Ricin, cancer)
virus
Metal ions
pH
Method
toxins
bacteria
Organic cofactors
The success on designing sensors for one target (e.g., pH) cannot be
translated into success for designing sensors for other target analytes.
Until recently, antibody is the only method that is general enough for a broad
range of targets, but antibodies are not very good at sensing small molecular
metabolites and biomarkers.
Functional DNA as selective contrast agents
RNA
DNA
O
5'
A
O
O
DNA/RNA = Protein enzymes
DNA/RNA = Antibodies
A
O
2'
3'
H
O
O P O
OH
O
−
O P O
O
C
O
Substrate
−
C
O
M(II)
A: DNAzyme
O
Enzyme
H
O
OH
O
O P O−
+
O P O−
G
O
G
O
O
O
H
O
O P O
OH
O
−
O P O
T
O
B: Aptamer
U
O
O
O
H
O
O P O
O
−
C: Aptazyme
OH
O
−
O P O
O
−
M(II)
H
H
N
N H
N
O
N
N
N
H N
N
N H
O
T
N
N
N
N
A
H N
O
N H
O
G
C
H
Kruger, K. et al. Cell 31, 147 (1982).
Guerrier-Takada, C. et al. Cell 35, 849 (1983).
Breaker, R.; Joyce, G. Chem. Biol. 1, 223 (1994).
A general method to obtain DNA/RNA for a broad range of targets
In vitro selection
or SELEX (Systematic Evolution of Ligands by
Exponential Enrichment )
-----effective against both small and large
molecular targets
Molecules recognized by selected DNA/RNA
High throughput (1014-1015
different sequences)
• Selective Amplification
• Improvement in each round
• Minimal cost (~ $5/round)
• Short time (~ 2 days/round)
A. D. Ellington, J. W. Szostak, Nature 1990, 346, 818.
C. Tuerk, L. Gold Science 1990, 249, 505.
A. Beaudry, G. F. Joyce, Science 1992, 257, 635.
Metal ions (Mg2+, Ca2+, Pb2+, Co2+, Cu2+, Hg2+, U(VI)
Organic dyes (Cibacron blue, reactive green 19)
Amino acids (L-Valine, D-Tryptophan)
Nucleosides/nucleotides (Guanosine, ATP)
Nucleotide analogs (8-oxo-dG, 7-Me-guanosine)
Biological cofactors (NAD, porphyrins, Vitamin B12)
Aminoglycosides (Tobramycin, Neomycin)
Antibiotics (Streptomycin, Viomycin)
Peptides (Rev peptide)
Enzymes (Human Thrombin, HIV Rev Transcriptase)
Growth cofactors (Karatinocyte and Basic fibroblast)
Antibodies (human IgE)
Gene regulatory factors (elongation factor Tu)
Cell adhesion molecules (human CD4, selectin)
Viral particles (Rous sarcoma virus, Anthrax spores)
J. Liu, Y. Lu, J. Fluoresc. 2004, 14, 343.
Examples of in vitro selected DNAzymes
3' N N N N N N Y rR N N N N N N N 5'
5' N N N N N N R
N N N N N N N 3'
A
G
G
G
C
C
T
A
A
A
G
C
CTA
3' N N N N N N G rN N N N N N N N 5'
5' N N N N N N T
N N N N N N N 3'
AA
C
C
G
G
G
A
G TC
G C
C
Mg2+
Pb2+
UO22+
Zn2+
5' Y Y Y Y A A T A C G N N N N N 3'
R R R R A C 3'
YYYY
C
CGG
C N N N N N 5'
T
G
Cu2+
Co2+
New metal-specific sites can be obtained in DNA, just like in proteins
Lu, Y. Chem. Euro. J. 8, 4588-4596 (2002).
Examples of in vitro selected DNAzymes
3' N N N N N N Y rR N N N N N N N 5'
5' N N N N N N R
N N N N N N N 3'
A
G
G
G
C
C
T
A
A
A
G
C
CTA
3' N N N N N N G rN N N N N N N N 5'
5' N N N N N N T
N N N N N N N 3'
AA
C
C
G
G
G
A
G TC
G C
C
UO22+
Mg2+
Pb2+
Substrate
M(II)
Enzyme
5' Y Y Y Y A A T A C G N N N N N 3'
R R R R A C 3'
YYYY
C
CGG
C N N N N N 5'
T
G
Cu2+
Similar secondary structures, making it easy for signal transduction.
Lu, Y. Chem. Euro. J. 8, 4588-4596 (2002).
Four key steps in designing imaging agents
√ a general method to obtain molecules for a specific
analyte;
?
a general method to improve selectivity;
What most want to do
What most end up doing
Problems with Selectivity in in vitro Selection
0.12
0.1
kobs (min-1)
0.5 mM Co(II)
0.08
0.5 mM Zn(II)
0.5 mM Pb(II)
0.06
0.04
0.02
0
No Negative Selection
•
•
Sequences selected with Co2+ show high activity with Zn(II) and Pb(II)
Must reduce or remove unwanted activity to improve metal selectivity
Initial pool of
DNA/RNA
2. A general method to
improve selectivity:
negative selection
Selections
using only Co2+
DNA/RNA with
2+
Co activity
Positive
Selection


Incorporate negative
selection to reduce
“unwanted” activity
Can be performed in
parallel with positive
selection for
comparison
Selection
using only Co
2+
Negative
Selection
Selection with a "metal
soup" containing
competing metal ions
Remove sequences that are
active with other metal ions
2+
High Co activity,
Continue Co2+ selection
2+
but with low Co
P. J. Bruesehoff, J. Li, A. J.
Augustine III, and Y. Lu,
Combinatorial Chemistry and
High Throughput Screening,
5, 327-335 (2002).
selectivity
High Co2+ activity with
2+
high Co selectivity
Improved Metal Ion Selectivity after
Negative Selection
0.25
0.2
0.5 mM Co(II)
kobs (min-1)
0.5 mM Zn(II)
0.15
0.5 mM Pb(II)
0.1
0.05
0
No Negative Selection
Negative Selection
P. J. Bruesehoff, J. Li, A. J. Augustine III, and Y. Lu, Combinatorial Chemistry
and High Throughput Screening, 5, 327-335 (2002).
Four key steps in designing imaging agents
√ a general method to obtain molecules for a specific
analyte;
√ a general method to improve selectivity;
? a general method to transform molecular
recognition into physical detectable signals without
compromising the binding affinity and selectivity;
Analytes
Signal
Target
Signal
recognition
transduction
part
part
Fluorescence
Color
An Ideal case of transforming binding into signals
Aptamer
Target
Reporter
A “general” replacement method: using a reporter
such as chromophore, fluorophore or electrochemical agent
An Ideal case of transforming binding into signals
A general replacement method: using a reporter
such as chromophore, fluorophore or electrochemical agent
What happened most cases
Because the reporter molecule is often (relatively large) organic molecules,
This method often result in loss of selectivity.
Solution: place the reporter away from the binding site
It often results in loss of coupling of binding with signal transduction
and thus loss of sensitivity
What most ends up doing:
It becomes a trial and error process…..
Examples of in vitro selected DNAzymes
3' N N N N N N Y rR N N N N N N N 5'
5' N N N N N N R
N N N N N N N 3'
A
G
G
G
C
C
T
A
A
A
G
C
CTA
3' N N N N N N G rN N N N N N N N 5'
5' N N N N N N T
N N N N N N N 3'
AA
C
C
G
G
G
A
G TC
G C
C
UO22+
Mg2+
Pb2+
Substrate
M(II)
Enzyme
5' Y Y Y Y A A T A C G N N N N N 3'
R R R R A C 3'
YYYY
C
CGG
C N N N N N 5'
T
G
Cu2+
Similar secondary structures, making it easy for signal transduction.
Lu, Y. Chem. Euro. J. 8, 4588-4596 (2002).
A general method to convert DNAzymes into fluorescent
sensors using catalytic beacon
cleavage site
substrate strand 17DS
3'- G T A G A G A A G G rN T A T C A C T C A -5'
5'- C A T C T C T T C T
A T A G T G A G T -3'
A A
C
C
G
G
T CG
A
G
enzyme strand 17E
C
G C
COO3' 5'
17DS
5'
17E
O
O
3'
O
P
TAMRA
O
O
O
N N
N
H
OH
N
Dabcyl
Fluorescent
tag
Hybridization
with catalytical DNA
Fluorescence
suppressed
rA
Catalytic DNA
strand
Quencher
Pb2+
rA
80000
fluorescence intensity
rA
Catalytic DNA
strand
H
N
O
O P O
O-
O-
RNA linkage
Substrate strand
N+
O
N
I
III
+Enz
60000
II
I
+Pb2+
40000
III
20000
II
0
570
600
630
660
Quencher
wavelength (nm)
Li, J.: Lu, Y. J. Am. Chem. Soc., 122, 10466-10467. (2000).
690
A Highly Sensitive and Selective DNAzyme Biosensor for Pb2+
Sensitivity
700
400
40
500
350
30
20
Pb2+
10
400
v fluo (counts/s)
vfluo (counts/s)
600
0
0
0.05
0.1
0.15
0.2
300
200
Co2+
100
0
0.001
300
250
200
150
100
intensity at 580 nm (counts)
Selectivity
50000
40000
Pb2+
30000
20000
M2+
10000
0
0
50
100
200
300
400
tim e (s)
0
0.01
0.1
1
10
100
Pb Co Zn Mn Ni Cd Cu Mg Ca
Pb(II) or Co (II) concentration (µ M)
Dynamic range: 1 nM (0.2 ppb) to 4 µM (800 ppb)
(Lead toxic level defined by US CDC: 500 nM (100 ppb))
(Lead toxic level defined by US EPA: 75 nM (15 ppb)
Li, J.; Lu, Y. J. Am. Chem. Soc.122, 10466-10467 (2000).
Liu, J.; Lu, Y. Anal. Chem. 75, 6666 – 6672 (2003).
Lu, Y. et al., Biosensors & Bioeletronics 18, 529-540 (2003).
Swearingen, C. B. et al., Anal. Chem. 77, 442-448 (2005).
A general method to convert DNAzymes into fluorescent sensors
using catalytic beacon for a broad range of metal ions
Fluorescent sensors
Based on catalytic beacon
Pb2+: Detection limit: 1 nM
EPA MCL:
75 nM
UO22+: Detection limit: 45 pM
EPA MCL:
126 nM
ICP-MS:
420 pM
Cu2+: Detection limit: 35 nM
EPA MCL:
20 μM
Hg2+: Detection limit: 2.4 nM
EPA MCL:
10 nM
Li, J.: Lu, Y. J. Am. Chem. Soc., 122, 10466-10467. (2000).
J. Liu, et al. Proc. Natl. Acad. Sci 104, 2056 (2007).
J. Liu and Y. Lu J. Am. Chem. Soc. 129, 9838 (2007).
J. Liu and Y. Lu, Angew. Chem., Int. Ed., 46,7587 (2007).
Molecular Beacon vs. Catalytic Beacon
M2+
Target
nalyte
Analyte
Target
Oligonucleotide
Molecular beacon
Can detect DNA/RNA only
No signal amplifications
Based on fluorescent intensity
Catalytic beacon
Can detect a broad range of targets
Signal amplifications
Based on fluorescent rate increase
S. Tyagi and F. R. Kramer, Nature Biotech. 14, 303-308 (1996).
J. Li and Y. Lu, J. Am. Chem. Soc. 122, 10466-10467 (2000).
High specificity or selectivity
Over 1 million fold selectivity over Th(IV),
and hundreds of millions fold selectivity over other metal ions
Juewen Liu, Andrea K. Brown, Xiangli Meng, Donald M. Cropek, Jonathan D. Istok, David B. Watson, and Yi Lu,
Proc. Natl. Acd. Sci. USA 104, 2056 (2007).
Colorimetric sensing based on DNAfunctionalized nanoparticles
DNA
Red
Blue
C. A. Mirkin, et al. Nature 382, 607-609 (1996).
R. Elghanian,et al. Science 277, 1078-1080 (1997).
Next Steps:
How to expand the technology beyond DNA detection?
Design of a Simple Colorimetric Biosensor
cleavage site
substrate strand 17DS
3'- G T A G A G A A G G rAPb
T A T C A C T C A -5'
5'- C A T C T C T T C T
A T A G T G A G T -3'
A A
C
C
G
G
T CG
A
G
enzyme strand17E
C
G C
BLUE
Mix
Aggregate
Pb
RED
Pb
17E
=
5'GGAAGAGATG
Au
=
Pb
BLUE
=
S
rA
-3' =
SubAu
5'-CACGAGTTGACA-3'
Pb
RED
= DNAAu
Liu, J.; Lu, Y. J. Am. Chem. Soc. 125, 6642-6643 (2003).
pH Indicator like Operation
0
0.3
0.5
5 µM Mg(II) Ca(II)
pH 9.5
Mn(II)
8.0
1
Co(II)
7.0
2
3
4
Ni(II)
Cu(II)
Zn(II)
4.0
3.0
2.0
Liu, J.; Lu, Y. J. Am. Chem. Soc. 125, 6642-6643 (2003).
Liu J.; Lu, Y. Chem. Mater., 16, 3231 (2004);
Liu J.; Lu, Y. J. Am. Chem. Soc. 126, 12298 (2004).
5 µM Pb(II)
Cd(II)
1.0
Four key steps in designing imaging agents
√ a general method to obtain molecules for a specific
analyte;
√
a general method to improve selectivity;
√
a general method to transform molecular
recognition into physical detectable signals without
compromising the binding affinity and selectivity;
?
a general method to fine-tune the dynamic range.
The need for tunable dynamic range
• 22 million old houses in the US alone have used lead paint
• US federal “thresholds” are 1.0 mg/cm2 and 0.5%
• Current lead detection kits are based on Na2S•9H2O or
sodium rhodizonate.
• A study of available kits showed low rates of both false positive
and false negative results when compared to laboratory
analytical results using the federal thresholds (www.hud.gov)
• Current kits cannot tune the dynamic range
Threshold
yes
Signal
yes
no
no
Lead concentration
IDEAL CURVE
Threshold
A Colorimetric Biosensor
with Tunable Dynamic Range
A. Active DNA
cleavage site
substrate strand 17DS
Extinction
1.5
A
B
1.0
0.5
0.0
3'- G T A G A G A A G G rA T A T C A C T C A -5'
450 550 650 750 450 550 650 750
Wavelength (nm)
Wavelength (nm)
5'- C A T C T C T T C T
A T A G T G A G T -3'
A A
C
C
G
G
T CG
A
G
enzyme strand17E
C
G C
15
C
12
cleavage site
substrate strand 17DS
3'- G T A G A G A A G G rA T A T C A C T C A -5'
5'- C A T C T C T T C C
A T A G T G A G T -3'
A A
C
C
G
G
T CG
A
G
enzyme strand17E
C
G C
E522/E700
B. Inactive DNA
9
B:A = 20:1
B:A = 0:1
6
3
0
0.01
0.1
1
[Pb(II)] µM
Brown, A. K.; Li, J.; Pavot, C. M.-B.; Lu, Y. Biochemistry 42, 7152-7161 (2003).
Liu, J.; Lu, Y. J. Am. Chem. Soc. 125, 6642-6643 (2003).
10
100
Pb2+ Detection in Paint
1.0 mg/cm2 (threshold)
qualitative
0
0.05
0.34
1.22
0.81
4.71
1.52
mg Pb / cm2 paint
10
8
Latex paint
Oil paint
7
Latex on latex
Oil on oil
Oil on Latex
Latex on Oil
8
A538/A700
A538/A700
6
5
4
3
6
4
2
2
1
Portable colorimeter
quantitative
0
0
0
1
2
mg/cm2 Pb
3
4
5
0
1
2
3
4
2
mg/cm Pb
5
6
7
The tunable sensor allowed our Pb sensor to change color
right at the federal threshold of 1.0 mg/cm2, and to work with
different types of paints.
Beyond metal and catalytic DNA-based detection
Metal ions (Mg(II), Ca(II), Pb(II), Zn(II))
Organic dyes (Cibacron blue, reactive green 19)
Amino acids (L-Valine, D-Tryptophan)
Nucleosides/nucleotides (Guanosine, ATP)
Nucleotide analogs (8-oxo-dG, 7-Me-guanosine)
Biological cofactors (NAD, FMN, porphyrins, Vitamin B12)
Aminoglycosides (Tobramycin, Neomycin)
Antibiotics (Streptomycin, Viomycin)
Peptides (Rev peptide)
Enzymes (Human Thrombin, HIV Rev Transcriptase)
Growth cofactors (Karatinocyte GF, Basic fibroblast GF)
Antibodies (human IgE)
Gene regulatory factors (elongation factor Tu)
Cell adhesion molecules (human CD4, selectin)
Intact viral particles (Rous sarcoma virus, Anthrax spores)
Juewen Liu and Yi Lu, J. Fluoresc. 14, 343-354 (2004).
Aptamer sensors based on binding only
Adenosine aptamer
Liu J.; Lu, Y. Angew. Chem., Int. Ed., 45, 90-94 (2006).
Liu, J.; Lu, Y. Nature Protocol 1, 246-252 (2006).
The method is general:
a colorimetric cocaine sensor
Liu J.; Lu, Y. Angew. Chem., Int. Ed., 45, 90-94 (2006).
Liu, J.; Lu, Y. Nature Protocol 1, 246-252 (2006).
A dipstick test using functional DNA
nanoparticles
Cocaine
Juewen Liu, Debapriya Mazumdar and Yi Lu, Angew. Chem., Int. Ed. 45, 7955 –7959 (2006).
Fluorescence (au)
Fluorescence imaging using quantum dots
A
2.0
1.5
B
+ Adenosine+Cocaine
+ Cocaine
+ Adenosine
Blank
+Cytidine
+Cytidine+uridine
D
C
1.0
0.5
0.0
500
550
600
λ (nm)
650
550
600
λ (nm)
650
550
λ (nm)
600
650
550
600
650
λ (nm)
J. Liu, H.-H. Lee, and Y. Lu, Anal. Chem. 79, 4120-4125 (2007).
Extension to other types of nanomaterials:
carbon nanotubes (excellent near IR fluorescence)
Biotinylated
DNAzyme, pH 8
MWNT-DNAzyme
Hybridized Composite
500
15
400
300
10
200
5
Turnover #
Consumed substrate DNA (microM)
MWNT-Streptavidin
Substrate DNA
100
0
0
200
400 600 800
Time (min)
0
1000 1200
Immobilized onto MWNTDNAzyme composite
In solution phase
kcat
0.83 ±0.07 /min
2.85 ±0.29 /min
KM
2.21 ±0.57 µM
2.60 ±0.80 µM
kcat /KM
0.38 /(min⋅µM)
1.10 /(min⋅µM)
Multiple turnover behavior was fit to the
integrated Michaelis-Menten equation.
Tae-Jin Yim, et al., J. Am. Chem. Soc. 127, 12200-12201 (2005).
Smart MRI agents for in vivo applications:
Functional DNA-directed assembly of supermagnetic iron
oxide nanoparticles:
M. Yigit, D. Mazumdar, H.-K. Kim, J. H. Lee, B. Odintsov, and Y. Lu ChemBioChem 8, 1675 -1678 (2007).
Mehmet Veysel Yigit, Debapriya Mazumdar, and Yi Lu, Bioconjugate Chem. 19, 412-417 (2008).
Theranostics: Imaging and therapy
Liposome
containing both
flurophores and
drugs
Cisplatin (anti-cancer drug)
fluorescence transmission overlay
1.2
MCF-7
LNCaP
(prostate
cancer
cells)
Cell viability
(breast cancer
cells)
1.0
0.8
0.6
0.4
0.2
0.0
Day 2
Day 4
Apt-lipo-cisPt/MCF
Day 2
Day 4
Ctrl-lipo-cisPt/MCF
Day 2
Day 4
Apt-lipo/MCF
Day 2
Day 4
Apt-lipo-cisPt/LNCaP
Zehui Cao, Rong Tong, Abhijit Mishra, Gerard C. L. Wong, Jianjun Cheng and Yi Lu, Angew Chemie Int. Ed. 48, 6494
–6498 (2009).
Functional DNA sensors
Juewen Liu, Zehui Cao, and Yi Lu, Chem. Rev. 109, 1948-1998 (2009).
Summary
 Selective imaging agents can bridge the gap between imaging
technologies and biology/medical sciences
 To obtain imaging agents for a broad range of targets, general
strategies have been developed to
•
•
•
•
to obtain molecular agents;
to improve selectivity;
to convert molecular recognition event into physically detectable signals;
to tune the dynamic range.
 The functional DNA is very versatile in coupling different imaging
tags for selective imaging:
• fluorescence imaging (fluorophore, carbon nanotubes and quantum dots)
• colorimetric (gold nanoparticles)
• MRI (supermagnetic iron oxide nanoparticles)
 The combination of functional DNA with liposome that encapsulate
both fluorophores and drugs allow imaging and therapy.
Acknowledgments
DNA/RNA Lab at UIUC
Collaborators
Margaret Shyr, Dr. Paul Braun (MatSE, UIUC)
Graduate Students:
Abhijit Mishra, Gerard C. L. Wong (MatSE, UIUC)
Ying He
Andrea K. Brown
Rong Tong and Jianjun Cheng (MatSE, UIUC)
Hannah Ihms
Peter J. Bruesehoff
Robert Barry, Dr. Pierre Wiltzius (Beckman, UIUC)
Tian Lan
Hee-Kyung Kim
Tae-Jin Yim, Dr. Jonathan S. Dordick (CheE, RPI)
Darius Brown
Jing Li
Carla B. Swearingen, Dr. Paul W. Bohn (Chem, UIUC)
Nandini Nagraj
Jung Heon Lee
Kashan A. Shaikh, Dr. Chang Liu (ECE, UIUC)
Eric Null
Juewen Liu
In-Hyoung Chang, Dr. Donald M. Cropek (CERL, DoD)
Zidong Wang
Kevin E. Nelson
Brian Wong
Daryl P. Wernette
Funding:
Weichen Xu
Mehmet V. Yigit
NIH, DOE, NSF, DOD, HUD, EPA, & ISTC
Hang Xing
Debapriya Mazumdar
Yu Xiang
Seyed-Fakhreddin Torabi
Postdoctoral fellows:
Hui Wei
Zehui Cao
Juanzuo Zhou
Geng Lu
Xiangli Meng
Daisuke Miyoshi
Wenchao Zheng