TSPO targeted dendrimer imaging agent: synthesis, characterization, and cellular internalization.
While it has become common practice for dendrimers to deliver imaging and therapeutic agents, there are few reported examples of cellular internalization of dendrimers. Moreover, targeting of dendrimers to the mitochondria in cells has not yet been reported. Previously, we have delivered small molecule imaging agents into glioma and breast cancer cells by targeting the translocator protein (TSPO; formerly known as the peripheral benzodiazepine receptor or PBR) with a family of high-affinity conjugable ligands. The 18 kDa multimeric TSPO is expressed in steroid-producing cells, primarily on the outer mitochondrial membrane. This protein is a prime candidate for molecular targeting because tumors and other disease-related cells contain high densities of TSPO. Here, we present the synthesis, characterization, and cellular internalization into C6 rat glioma cells of a TSPO targeted dendrimer imaging agent.
Department of Chemistry, The Vanderbilt Institute for Chemical Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University, VU Station B 351822 Nashville, Tennessee 37235-1822, USA.
Lynn E
LE
Samuelson
Madeline J
MJ
Dukes
Colette R
CR
Hunt
Jonathan D
JD
Casey
Darryl J
DJ
Bornhop
D000818:Animals; D002463:Cell Membrane Permeability; D050091:Dendrimers / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003952:Diagnostic Imaging / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000175:diagnosis / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D051381:Rats; D018079:Receptors, GABA / Q000032:analysis* / Q000378:metabolism
D050091:Dendrimers; D004337:Drug Carriers; D024101:Mitochondrial Proteins; D018079:Receptors, GABA; C499229:TSPO protein, human