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1.
Bioconjug Chem ; 17(5): 1141-50, 2006.
Article in English | MEDLINE | ID: mdl-16984121

ABSTRACT

Liposomes have been a main focus of tumor-selective boron delivery strategies in boron neutron capture therapy (BNCT), a binary method for the treatment of cancer that is based on the nuclear reaction between boron atoms and low-energy thermal neutrons. Three novel carboranyl cholesterol derivatives were prepared as lipid bilayer components for the construction of nontargeted and receptor-targeted boronated liposomes for BNCT. A major structural feature of these novel boronated cholesterol mimics is the replacement of the B and the C ring of cholesterol with a carborane cluster. Computational analyses indicated that all three boronated compounds have structural features and physicochemical properties that are very similar to those of cholesterol. One of the synthesized boronated cholesterol mimics was stably incorporated into non-, folate receptor (FR)-, and vascular endothelial growth factor receptor-2 (VEGFR-2)-targeted liposomes. No major differences were found in appearance, size distribution, and lamellarity between conventional dipalmitoylphosphatidylcholine (DPPC)/cholesterol liposomes, nontargeted, and FR-targeted liposomal formulations of this carboranyl cholesterol derivative. FR-targeted boronated liposomes were taken up extensively in FR overexpressing KB cells in vitro, and the uptake was effectively blocked in the presence of free folate. In contrast, a boronated cholesterol mimic incorporated into nontargeted liposomes showed significantly lower cellular uptake. There was no apparent in vitro cytotoxicity in FR overexpressing KB cells and VEGFR-2 overexpressing 293/KDR cells when these were incubated with boronated FR- and (VEGFR-2)-targeted liposomes, respectively, although the former accumulated extensively in KB cells and the latter effectively interacted with VEGFR-2 by causing autophosphorylation and protecting 293/KDR cells from SLT (Shiga-like toxin)-VEGF cytotoxicity.


Subject(s)
Boron Compounds/metabolism , Boron Neutron Capture Therapy/methods , Cholesterol , Liposomes/metabolism , Boron Compounds/chemistry , Cell Line , Cholesterol/chemistry , Cholesterol/metabolism , Humans , Liposomes/chemistry , Models, Molecular , Molecular Structure , Neoplasms/therapy , Particle Size , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism
2.
Environ Sci Technol ; 39(15): 5689-93, 2005 Aug 01.
Article in English | MEDLINE | ID: mdl-16124303

ABSTRACT

Total gaseous mercury in headspace air was measured for enclosed concretes dry curing at 40 degrees C for intervals of 2, 28, and 56 days. Release of mercury was confirmed for ordinary Portland cement concrete (OPC) and three concretes in which class F fly ash substituted for a fraction of the cement: (a) 33% fly ash (FA33), (b) 55% fly ash (FA55), and (c) 33% fly ash plus 0.5% mercury-loaded powdered activated carbon (HgPAC). Mean rates of mercury release (0.10-0.43 ng/day per kg of concrete) over the standard first 28 days of curing followed the order OPC < FA33 approximately FA55 < HgPAC. The mercury flux from exposed surfaces of these concretes ranged from 1.9 +/- 0.5 to 8.1 +/-2.0 ng/m(2)/h, values similar to the average flux for multiple natural substrates in Nevada, 4.2 +/- 1.4 ng/m(2)/h, recently published by others. Air sampling extending for 28 days beyond the initial 28-day maturation for OPC, FA55, and HgPAC suggested that the average Hg release rate by OPC is constant over 56 days and that mercury release rates for FA55 and HgPAC may ultimately diminish to levels exhibited by OPC concrete. The release of mercury from all samples was less than 0.1% of total mercury content over the initial curing period, implying that nearly all of the mercury was retained in the concrete.


Subject(s)
Air Pollutants/analysis , Carbon/chemistry , Construction Materials/analysis , Gases/analysis , Mercury Compounds/analysis , Coal Ash , Particulate Matter , Time Factors
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