title: Noncovalent functionalization of carbon nanovectors with an antibody enables targeted drug delivery.
abstract: Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and thereby deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through noncovalent interactions. Such noncovalent assembly could enable high-throughput screening of drug/antibody combinations.
authors: Department of Chemistry, Rice University, MS-222, 6100 Main Street, Houston, Texas 77005, USA.
authors: Jacob M
authors: JM
authors: Berlin
authors: Tam T
authors: TT
authors: Pham
authors: Daisuke
authors: D
authors: Sano
authors: Khalid A
authors: KA
authors: Mohamedali
authors: Daniela C
authors: DC
authors: Marcano
authors: Jeffrey N
authors: JN
authors: Myers
authors: James M
authors: JM
authors: Tour
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized; D002244:Carbon / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004337:Drug Carriers; D011092:Polyethylene Glycols; D002244:Carbon; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab