Our Group's research mainly
focuses on fundamental understanding of
physiology in the nano regime and
further applying the newly discovered
physiological principles to address the
challenges in early disease diagnosis and
treatment.
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(I) Nano-bio interactions in vivo
a. Glomerular
filtration of few-atom gold nanoclusters: Size
effect |
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Glomerular
filtration
barrier behaves
as an atomically
precise
‘bandpass’
filter to
significantly
slow down renal
clearance of
few-atom gold
nanoclusters (AuNCs)
with the same
surface ligands
but different
sizes (Au18,
Au15 and
Au10-11).Compared
to Au25,
just few-atom
decreases in
size result in
four-to-nine
fold reductions
in renal
clearance efficiency
in the early
elimination
stage, because
the smaller
AuNCs are more
readily trapped
by the
glomerular
glycocalyx than
larger ones.
Recent Publications:
Bujie
Du, Xingya
Jiang,
Anindita Das,
Qinhan Zhou,
Mengxiao Yu,
Rongchao Jin,
Jie Zheng,
Nature
Nanotechnology,
2017 DOI:
10.1038/nnano.2017.170
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b. In
vivo transport of renal
clearable metal nanoparticles in the kidneys: Margination
effect |
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Lower-density
NPs
are
more
easily
distributed
in
the
body
and
have
shorter
retention
times
in
highly
permeable
organs
than
higher-density
NPs. The
density-dependent
in
vivo
behavior
of
metal
NPs
likely
results
from
their
distinct
margination
in
laminar
blood
flow,
which
opens
up
a new
path
for
precise
control
of
nanomedicines
in
vivo.
Recent Publications:
Tang, S., Peng, C., Xu, J., Du, B., Wang, Q.,
Vinluan, R. D., Yu, M., Kim, M.J., Zheng, J.
Tailoring Renal Clearance and Tumor Targeting of
Ultrasmall Metal Nanoparticles with Particle
Density.
Angew. Chem. Int. Ed.,
2016, 55, 16039-16043.
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c. Tumor
microenvironment:
Vasculature
and
Acidity
Effects |
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Increased
tumor
acidity
indeed
enhanced
the
uptake
of
AuNPs
with
acidity
targeting, but
only
for
a limited
period
of
time. By
making
use
of
simple
surface
chemistry,
these
two
effects
can
be
synchronized
in
time
for
high
tumor
targeting, opening
new
possibilities
to
further
improve
the
targeting
efficiencies
of
nanomedicines.
Recent Publications:
Yu, M.,
Zhou, C., Liu, L., Zhang, S., Sun, S., Hankins,
J.D., Sun, X. and Zheng, J., 2017. Interactions
of Renal-Clearable Gold Nanoparticles with Tumor
Microenvironments: Vasculature and Acidity
Effects.
Angewandte Chemie, 129(15),
pp.4378-4383.
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(II)
Biomedical applications of
renal clearable metal nanoparticles
a.
Cancer imaging
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To investigate
whether renal
clearable metal
NPs can target
and image tumors
with poor
permeability, we
used an
orthotopic
murine glioma
model to
investigate the
passive
targeting of 3
nm renal
clearable gold
nanoparticles (AuNPs)
and found out
that 3-nm AuNPs
were able to
target
intracranial
tumor tissues
with higher
efficiency (2.3×
relative to
surrounding
non-tumor normal
brain tissues)
and greater
specificity
(3.0×) than did
the larger AuNPs
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Recent Publications:
Peng, C., Gao,
X., Xu, J., Du, B., Ning, X., Tang, S., Bachoo,
R.M., Yu, M., Ge, W.P. and Zheng, J., 2017.
Targeting orthotopic gliomas with
renal-clearable luminescent gold nanoparticles.
Nano
Research,
4(10),
pp.1366-1376.
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b.Noninvasive fluorescence kidney
functional imaging |
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To address the
long-standing challenge in noninvasive
fluorescence kidney imaging, we are developing
renal clearable metal nanoparticles for
noninvasive imaging of kidney function and
noninvasive staging of kidney dysfunction.
Recent
Publications:
(1) M. X.
Yu, J. C. Zhou, B. J. Du, X. H. Ning, C.
Authement, L. Gandee, P. Kapur, J. T. Hsieh, J.
Zheng. “Noninvasive Staging of Kidney
Dysfunction Enabled by Renal Clearable
Luminescent Gold Nanoparticles”, Angew.
Chem. Int. Ed., 55, 2787-2791 (2016)
(Highlighted as VIP).
(2) M. X.
Yu, J. B. Liu, X. H. Ning, J. Zheng*.
“High-contrast Noninvasive Imaging of Kidney
Clearance Kinetics Enabled by Renal Clearable
Nanofluorophores”. Angew. Chem. Int. Ed.,
2015, 54, 15434-15438
(3) M.
X. Yu, J. Zheng*. “Clearance Pathways and Tumor
Targeting of Imaging Nanoparticles”.
ACS Nano, 2015, 9, 6655–6674.
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c.
Multimodality in vivo Imaging |
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To minimize nanotoxicity, we have developed a
class of luminescent metal nanoparticles that
can be cleared from the body through urinary
system but still serve as a new generation of
contrast agents for early disease diagnosis.
Recent Publications:
(1) J. Xu, M. Yu, P. Carter A, E. Hernandez, A.
Dang, P. Kapur, J. T. Hsieh, J. Zheng. "In Vivo
X-ray Imaging of Transport of Renal Clearable
Gold Nanoparticles in the Kidneys",
Angew. Chem. Int. Ed.,
2017,
DOI:
10.1002/anie.201707819
(online)
(Highlighted as VIP)
(2)
J. Liu, M.
Yu, C. Zhou, S. Yang, X. Ning, and J. Zheng,
“Passive Tumor Targeting of Renal Clearable
Luminescent Gold Nanoparticles: Long Tumor
Retention and Fast Normal Tissue Clearance”,
J. Am. Chem. Soc.,
2013, 135(13), 4978-4981.
(3)
C. Zhou, G. Hao, T. Patrick, J. Liu, M.
Yu, S. Sun, O. Oz, X. Sun, and J. Zheng, “Near
Infrared Emitting Radioactive Gold Nanoparticles
with Molecular Pharmacokinetics”,
Angew. Chem. Int. Ed.,
2012, 51(40), 10118-10122.
(4)
C. Zhou, M. Long, Y. Qin,
X. Sun and J. Zheng, “Luminescent Gold
Nanoparticles with Efficient Renal Clearance”,
Angew. Chem. Int. Ed.,
2011, 50(14), 3168-3172.
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d.
Targeting acidic
tumor
microenvironment
and cancer
receptor
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By taking advantage of robust single-particle fluorescence and
giant Raman enhancements of unique polycrystalline silver NPs (AgNPs), we found
specific c-RGD peptide−αvβ3 integrin interactions not only induced endosome formation more rapidly, enhanced constrained diffusion, but also minimized nonspecific chemical interactions between the NPs and intracellular biomolecules than passive PEGylation chemistry.
By coating luminescent gold nanoparticles with a natural peptide, glutathione, and the simplest stable aminothiol, cysteamine, we enabled the nanoparticles to exhibit not only high resistance to serum protein adsorption but also pH-dependent adsorption onto live cell membranes in the presence of serum proteins.
Recent Publications:
(1)
S. Sun, X. Ning, G.
Zhang, Y.C. Wang, C. Peng, J. Zheng. "Dimerization
of Organic Dyes on Luminescent Gold
Nanoparticles for Ratiometric pH Sensing", Angew. Chem. Int. Ed.,
2016,
55,
2421
–2424.
(2)
S. Sun, C. Zhou, S. Chen, J.B. Liu, J. Yu, J. Chilek, L. Zhao,
M.X. Yu, R. Vinluan, B. Huang, and J. Zheng, "Surface-Chemistry Effect on
Cellular Response of Luminescent Plasmonic Silver Nanoparticles",
Bioconjugate Chemistry, 2014, DOI: 10.1021/bc500008a.
(3) M. Yu,† C. Zhou,†
J. Liu, J. D. Hankins, J. Zheng, “Luminescent Gold Nanoparticles with pH
De-pendent Membrane Adsorption”,
J. Am. Chem. Soc.,
133, 11014-11017 (2011).
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