title: 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 excellent substrate for heparitinase enzyme, as evidenced by ~70% recovery of fluorescence from the dye upon heparitinase treatment. However, the presence of OSCS results in diminished fluorescence recovery from the nanosensor upon heparitinase treatment, as the enzyme is inhibited by the contaminant. The newly designed nanosensor can detect as low as 1 × 10(-9) % (w/w) OSCS making it the most sensitive tool to date for the detection of trace amounts of OSCS in pharmaceutical heparins.
authors.affiliation: Departments of Medicinal Chemistry and Bioengineering, University of Utah , Salt Lake City, Utah 84112, United States.
authors.forename: Mausam
authors.initials: M
authors.lastname: Kalita
authors.forename: Sivasai
authors.initials: S
authors.lastname: Balivada
authors.forename: Vimal Paritosh
authors.initials: VP
authors.lastname: Swarup
authors.forename: Caitlin
authors.initials: C
authors.lastname: Mencio
authors.forename: Karthik
authors.initials: K
authors.lastname: Raman
authors.forename: Umesh R
authors.initials: UR
authors.lastname: Desai
authors.forename: Deryl
authors.initials: D
authors.lastname: Troyer
authors.forename: Balagurunathan
authors.initials: B
authors.lastname: Kuberan
mesh_terms: D000925:Anticoagulants / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000032:analysis*; D004396:Coloring Agents / Q000737:chemistry*; D004340:Drug Contamination; D031541:Fluorescence Resonance Energy Transfer; D006046:Gold / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000295:instrumentation; D010316:Particle Size; D013499:Surface Properties
chemical_list: D000925:Anticoagulants; D004396:Coloring Agents; D006046:Gold; D006493:Heparin; D002809:Chondroitin Sulfates