Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo.
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. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, cetuximab. This construct is unusual in that all three components are assembled through noncovalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development.
Department of Head and Neck Surgery, Unit 441, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Daisuke
D
Sano
Jacob M
JM
Berlin
Tam T
TT
Pham
Daniela C
DC
Marcano
David R
DR
Valdecanas
Ge
G
Zhou
Luka
L
Milas
Jeffrey N
JN
Myers
James M
JM
Tour
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002244:Carbon / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000737:chemistry*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004337:Drug Carriers; D011092:Polyethylene Glycols; D002244:Carbon; D017239:Paclitaxel; D000068818:Cetuximab