Details
| Original language | English |
|---|---|
| Pages (from-to) | 2453-2460 |
| Number of pages | 8 |
| Journal | Bioconjugate Chemistry |
| Volume | 22 |
| Issue number | 12 |
| Early online date | 17 Nov 2011 |
| Publication status | Published - 21 Dec 2011 |
| Externally published | Yes |
Abstract
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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Chemical Engineering(all)
- Bioengineering
- Engineering(all)
- Biomedical Engineering
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
- Chemistry(all)
- Organic Chemistry
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In: Bioconjugate Chemistry, Vol. 22, No. 12, 21.12.2011, p. 2453-2460.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Fluorescence imaging with multifunctional polyglycerol sulfates
T2 - Novel polymeric near-IR probes targeting inflammation
AU - Licha, Kai
AU - Welker, Pia
AU - Weinhart, Marie
AU - Wegner, Nicole
AU - Kern, Sylvia
AU - Reichert, Stefanie
AU - Gemeinhardt, Ines
AU - Weissbach, Carmen
AU - Ebert, Bernd
AU - Haag, Rainer
AU - Schirner, Michael
PY - 2011/12/21
Y1 - 2011/12/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84555188482&partnerID=8YFLogxK
U2 - 10.1021/bc2002727
DO - 10.1021/bc2002727
M3 - Article
C2 - 22092336
AN - SCOPUS:84555188482
VL - 22
SP - 2453
EP - 2460
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 12
ER -