Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo

ACS Nano. 2012 Mar 27;6(3):2497-505. doi: 10.1021/nn204885f. Epub 2012 Feb 16.

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. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Carbon / chemistry*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cell Line, Tumor
  • Cetuximab
  • Combined Modality Therapy
  • Drug Carriers / chemistry*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Mice
  • Nanostructures / chemistry*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Polyethylene Glycols / chemistry
  • Tumor Burden / drug effects
  • Tumor Burden / radiation effects

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Drug Carriers
  • Polyethylene Glycols
  • Carbon
  • Paclitaxel
  • Cetuximab