title: Drug nanocarriers labeled with near-infrared-emitting quantum dots (quantoplexes): imaging fast dynamics of distribution in living animals.
abstract: The knowledge of the biodistribution of macromolecular drug formulations is a key to their successful development for specific tissue- and tumor-targeting after systemic application. Based on the polyplex formulations, we introduce novel drug nanocarriers, which we denote as "quantoplexes" incorporating near-infrared (IR)-emitting cadmium telluride (CdTe) quantum dots (QDs), polyethylenimine (PEI), and a macromolecular model drug [plasmid DNA (pDNA)], and demonstrate the ability of tracking these bioactive compounds in living animals. Intravenous application of bare QD into nude mice leads to rapid accumulation in the liver and peripheral regions resembling lymph nodes, followed by clearance via the liver within hours to days. Quantoplexes rapidly accumulate in the lung, liver, and spleen and the fluorescent signal is detectable for at least a week. Tracking quantoplexes immediately after intravenous injection shows rapid redistribution from the lung to the liver within 5 minutes, depending on the PEI topology and quantoplex formulation used. With polyethyleneglycol (PEG)-modified quantoplexes, blood circulation and passive tumor accumulation was measured in real time. The use of quantoplexes will strongly accelerate the development of tissue and tumor-targeted macromolecular drug carriers.
authors.affiliation: Center for Drug Research, Department of Pharmacy, Pharmaceutical Biology-Biotechnology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Arkadi
authors.initials: A
authors.lastname: Zintchenko
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Susha
authors.forename: Massimo
authors.initials: M
authors.lastname: Concia
authors.forename: Jochen
authors.initials: J
authors.lastname: Feldmann
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Rogach
authors.forename: Manfred
authors.initials: M
authors.lastname: Ogris
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D008099:Liver / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D010957:Plasmids / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000737:chemistry; D045663:Quantum Dots; D019265:Spectroscopy, Near-Infrared; D013691:Tellurium / Q000737:chemistry
chemical_list: D019187:Cadmium Compounds; D004337:Drug Carriers; D011094:Polyethyleneimine; D013691:Tellurium; C028337:cadmium telluride
references.citation: J Gene Med. 2002 Jan-Feb;4(1):84-91
references.pmid: 11828391
references.citation: J Pharm Sci. 2008 Jan;97(1):237-50
references.pmid: 17721944
references.citation: Nat Protoc. 2008;3(1):89-96
references.pmid: 18193025
references.citation: Bioconjug Chem. 2005 Jul-Aug;16(4):785-92
references.pmid: 16029019
references.citation: Mol Ther. 2002 Apr;5(4):463-72
references.pmid: 11945074
references.citation: Bioconjug Chem. 1992 Nov-Dec;3(6):533-9
references.pmid: 1463783
references.citation: Nat Biotechnol. 2004 Jan;22(1):47-52
references.pmid: 14704706
references.citation: Am J Respir Cell Mol Biol. 2002 Aug;27(2):151-9
references.pmid: 12151306
references.citation: Hum Gene Ther. 2008 Nov;19(11):1283-92
references.pmid: 19866491
references.citation: Anal Biochem. 2002 Mar 1;302(1):75-80
references.pmid: 11846378
references.citation: Mol Ther. 2000 Dec;2(6):649-56
references.pmid: 11124067
references.citation: J Gene Med. 2004 Oct;6(10):1102-11
references.pmid: 15386739
references.citation: Nat Med. 2007 Mar;13(3):372-7
references.pmid: 17322898
references.citation: Nat Biotechnol. 2007 Oct;25(10):1165-70
references.pmid: 17891134
references.citation: J Control Release. 2007 Mar 12;118(1):118-25
references.pmid: 17250923
references.citation: Nat Biotechnol. 2004 Jan;22(1):93-7
references.pmid: 14661026
references.citation: Bioconjug Chem. 2008 May;19(5):983-7
references.pmid: 18429627
references.citation: Gene Ther. 2008 Aug;15(16):1131-8
references.pmid: 18528432
references.citation: Bioconjug Chem. 2003 Jan-Feb;14(1):222-31
references.pmid: 12526712
references.citation: Nat Biotechnol. 2008 Jan;26(1):83-90
references.pmid: 18157119
references.citation: Bioconjug Chem. 2007 Mar-Apr;18(2):389-96
references.pmid: 17263568
references.citation: Small. 2009 Sep;5(17):1997-2004
references.pmid: 19466710
references.citation: Nat Rev Drug Discov. 2003 May;2(5):347-60
references.pmid: 12750738
references.citation: Gene Ther. 1999 Apr;6(4):595-605
references.pmid: 10476219
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15549-54
references.pmid: 17875985
references.citation: Nano Lett. 2007 Nov;7(11):3452-61
references.pmid: 17949046
references.citation: J Gene Med. 2004 Feb;6 Suppl 1:S45-53
references.pmid: 14978750
references.citation: Nat Mater. 2005 Jun;4(6):435-46
references.pmid: 15928695