title: Targeted killing of cancer cells in vivo and in vitro with EGF-directed carbon nanotube-based drug delivery.
abstract: Carbon nanotube-based drug delivery holds great promise for cancer therapy. Herein we report the first targeted, in vivo killing of cancer cells using a drug-single wall carbon nanotube (SWNT) bioconjugate, and demonstrate efficacy superior to nontargeted bioconjugates. First line anticancer agent cisplatin and epidermal growth factor (EGF) were attached to SWNTs to specifically target squamous cancer, and the nontargeted control was SWNT-cisplatin without EGF. Initial in vitro imaging studies with head and neck squamous carcinoma cells (HNSCC) overexpressing EGF receptors (EGFR) using Qdot luminescence and confocal microscopy showed that SWNT-Qdot-EGF bioconjugates internalized rapidly into the cancer cells. Limited uptake occurred for control cells without EGF, and uptake was blocked by siRNA knockdown of EGFR in cancer cells, revealing the importance of EGF-EGFR binding. Three color, two-photon intravital video imaging in vivo showed that SWNT-Qdot-EGF injected into live mice was selectively taken up by HNSCC tumors, but SWNT-Qdot controls with no EGF were cleared from the tumor region in <20 min. HNSCC cells treated with SWNT-cisplatin-EGF were also killed selectively, while control systems that did not feature EGF-EGFR binding did not influence cell proliferation. Most significantly, regression of tumor growth was rapid in mice treated with targeted SWNT-cisplatin-EGF relative to nontargeted SWNT-cisplatin.
authors.affiliation: Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, USA.
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Bhirde
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Julie
authors.initials: J
authors.lastname: Gavard
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Alioscka A
authors.initials: AA
authors.lastname: Sousa
authors.forename: Andrius
authors.initials: A
authors.lastname: Masedunskas
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leapman
authors.forename: Roberto
authors.initials: R
authors.lastname: Weigert
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.forename: James F
authors.initials: JF
authors.lastname: Rusling
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry*; D013379:Substrate Specificity; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D037742:Nanotubes, Carbon; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D002945:Cisplatin