Targeted killing of cancer cells in vivo and in vitro with IGF-IR antibody-directed carbon nanohorns based drug delivery

Int J Pharm. 2015 Jan 30;478(2):644-54. doi: 10.1016/j.ijpharm.2014.12.015. Epub 2014 Dec 12.

Abstract

Oxidized single-wall carbon nanohorns (oxSWNHs) have shown great potential in drug delivery. The purpose of this study was to design an effective targeted drug delivery system (DDS) based on oxSWNHs, which could carry high dose of drug to tumor sites and improve the therapeutic efficacy with less adverse effects. OxSWNHs incorporated the anticancer drug vincristine (VCR) via physical adsorption, then wrapped DSPE-PEG-IGF-IR monoclonal antibody (mAb) through an amide liker to obtain the drug delivery system, VCR@oxSWNHs-PEG-mAb. The in vitro release behavior study indicated that the DDS had good sustained release and the cumulative release of VCR was 80% at 144h. Compared with free VCR, the tumor targeting drug delivery efficiently enhanced the cytotoxicity in cultured MCF-7 cells in vitro, and afforded higher antitumor efficacy without obvious toxic effects to normal organs in tumor mice in vivo. In addition, the targeted DDS could reduce the toxicity of VCR to the living mice. This study demonstrated that VCR@oxSWNHs-PEG-mAb might be promising for high treatment efficacy with minimal side effects in future cancer therapy.

Keywords: Antitumor efficiency; Drug delivery system; IGF-IR monoclonal antibody; Oxidized single-wall carbon nanohorn; Vincristine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / chemistry
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Carbon / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Delivery Systems
  • Drug Liberation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MCF-7 Cells
  • Male
  • Mice, Inbred ICR
  • Nanostructures / administration & dosage*
  • Nanostructures / chemistry
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Receptor, IGF Type 1 / immunology*
  • Tumor Burden / drug effects
  • Vincristine / administration & dosage*
  • Vincristine / chemistry

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Phosphatidylethanolamines
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Vincristine
  • Carbon
  • Receptor, IGF Type 1