Fluorescence Imaging with
Multifunctional Polyglycerol
Sulfates: Novel Polymeric near-IR Probes Targeting Inflammation
Posted on 2011-12-21 - 00:00
We present a highly selective approach for the targeting
of inflammation
with a multivalent polymeric probe. Dendritic polyglycerol was employed
to synthesize a polyanionic macromolecular conjugate with a near-infrared
fluorescent dye related to Indocyanine Green (ICG). On the basis of
the dense assembly of sulfate groups which were generated from the
polyol core, the resulting polyglycerol sulfate (molecular weight
12 kD with ∼70 sulfate groups) targets factors of inflammation
(IC50 of 3–6 nM for inhibition of L-selectin binding)
and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging
in an animal model of rheumatoid arthritis demonstrated fast and selective
uptake which enabled the differentiation of diseased joints (score
1–3) with a 3.5-fold higher fluorescence level and a signal
maximum at 60 min post injection. Localization in tissues using fluorescence
histology showed that the conjugates are deposited in the inflammatory
infiltrate in the synovial membrane, whereas nonsulfated control was
not detected in association with disease. Hence, this type of polymeric
imaging probe is an alternative to current bioconjugates and provides
future options for targeted imaging and drug delivery.
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Licha, Kai; Welker, Pia; Weinhart, Marie; Wegner, Nicole; Kern, Sylvia; Reichert, Stefanie; et al. (2016). Fluorescence Imaging with
Multifunctional Polyglycerol
Sulfates: Novel Polymeric near-IR Probes Targeting Inflammation. ACS Publications. Collection. https://doi.org/10.1021/bc2002727
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AUTHORS (11)
KL
Kai Licha
PW
Pia Welker
MW
Marie Weinhart
NW
Nicole Wegner
SK
Sylvia Kern
SR
Stefanie Reichert
IG
Ines Gemeinhardt
CW
Carmen Weissbach
BE
Bernd Ebert
RH
Rainer Haag
MS
Michael Schirner
KEYWORDS
Multifunctional Polyglycerol Sulfatesimaging probepolyglycerol sulfatefuture options60 min post injectionsulfate groupsDendritic polyglycerolinflammationanimal modelvivo accumulationweight 12 kDfluorescence histologytargets factorsnonsulfated controlIC 50Indocyanine GreenconjugateFluorescence Imagingpolyol coredrug deliveryICGfluorescence levelsynovial membrane