2014
DOI: 10.1021/ja409170z
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A Nanosensor for Ultrasensitive Detection of Oversulfated Chondroitin Sulfate Contaminant in Heparin

Abstract: Heparin has been extensively used as an anticoagulant for the last eight decades. Recently, the administration of a contaminated batch of heparin caused 149 deaths in several countries including USA, Germany, and Japan. The contaminant responsible for the adverse effects was identified as oversulfated chondroitin sulfate (OSCS). Here, we report a rapid, ultrasensitive method of detecting OSCS in heparin using a nanometal surface energy transfer (NSET) based gold-heparin-dye nanosensor. The sensor is an excelle… Show more

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Cited by 48 publications
(46 citation statements)
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References 28 publications
(38 reference statements)
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“…As described above, 1 exhibited some FXII activation; oversulfated chondroitin sulfates (OSCSs) exhibit this effect, and such a side effect may cause acute hypersensitivity reactions and endanger the lives of patients (28)(29)(30). Compared with 1, low concentrations of 2 exhibited significantly reduced FXII activation, whereas high concentrations (>16 μg/mL) of 2 and 8 still activated FXII.…”
Section: Compounds 5-8 Exhibit Strong Anticoagulant Activities By Selmentioning
confidence: 94%
“…As described above, 1 exhibited some FXII activation; oversulfated chondroitin sulfates (OSCSs) exhibit this effect, and such a side effect may cause acute hypersensitivity reactions and endanger the lives of patients (28)(29)(30). Compared with 1, low concentrations of 2 exhibited significantly reduced FXII activation, whereas high concentrations (>16 μg/mL) of 2 and 8 still activated FXII.…”
Section: Compounds 5-8 Exhibit Strong Anticoagulant Activities By Selmentioning
confidence: 94%
“…This construct proved to be a good substrate for heparinase, and the resulting release of the dye from the nanoparticle allowed recovery of fluorescence (otherwise quenched in the nanoparticle), which was exploited for analytical purposes. The presence of OSCS in the heparin samples resulted in diminished fluorescence recovery because heparinase activity is inhibited by such contaminants …”
Section: Heparin and Heparan Sulfatementioning
confidence: 99%
“…Since the 1990s, porcine mucosa has been the sole source of heparin in western countries because of potential prion contamination and the risk of infection with bovine spongiform encephalopathy. In late 2007 and early 2008, contamination of porcine heparin from China with an ''unnatural'' fully O-sulfated chondroitin sulfate [19][20] resulted in adverse events, including fatalities. As a consequence, US authorities are considering the reintroduction of bovine heparin, which continues to be produced and used clinically in South American countries, in order to diversify the sourcing of heparin.…”
Section: Discussionmentioning
confidence: 99%