The study on the preparation and characterization of gene-loaded immunomagnetic albumin nanospheres and their anti-cell proliferative effect combined with magnetic fluid hyperthermia on GLC-82 cells

Drug Des Devel Ther. 2015 Dec 15:9:6445-60. doi: 10.2147/DDDT.S93481. eCollection 2015.

Abstract

As one of the most common malignant tumors, the clinical and socio-economic consequences of lung cancer are significant. Currently, surgery is the main treatment strategy for this disease, but the survival rates of lung cancer patients are not ideal due to the high recurrence rate of the disease. Therefore, many researchers are exploring new specific therapeutic methods that are highly curative and minimally cytotoxic to healthy tissues. To this end, albumin nanospheres simultaneously were loaded with super-paramagnetic iron oxide nanoparticles (as gene vector and anticancer gene), and plasmid pDONR223-IFNG, and modified with anti-EGFR monoclonal antibody cetuximab as therapy. Targeting agents, namely gene-loaded immunomagnetic albumin nanospheres (cetuximab [C225]-IFNG-IMANS), were prepared for targeted lung carcinoma cells (GLC-82 cell lines). Transmission electron microscopy images showed that the C225-IFNG-IMANS were successfully prepared, and the ability of the nanospheres to target GLC-82 cells in vitro was confirmed by Prussian blue staining, immunofluorescence experiments, and magnetic resonance imaging. Transfection photographs and agarose gel electrophoresis proved that pDONR223-IFNG could be encased in the albumin nanospheres. A Cell Counting Kit-8 assay showed that the combination therapy group had significantly more therapeutic effects on GLC-82 cells than other therapy groups. A flow cytometry assay showed that the apoptotic index of the combined treatment group was 67.68%, whereas the indices of the C225 group, gene therapy group, and magnetic fluid hyperthermia group were 12.2%, 16.34%, and 20.04% respectively. Therefore, the combination of thermal treatment, molecular targeted treatment, and gene treatment synergistically targets GLC-82 cells, and the use of C225-IFNG-IMANS as a gene or drug carrier offers a novel and promising approach for the treatment of lung cancer.

Keywords: magnetic nanoparticles; nano-drug; targeting gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / chemistry*
  • Albumins / metabolism
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cetuximab / chemistry
  • Cetuximab / metabolism
  • Cetuximab / pharmacology*
  • Drug Carriers
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Humans
  • Hypothermia, Induced*
  • Imines / chemistry
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / chemistry*
  • Microscopy, Electron, Transmission
  • Polyethylenes / chemistry
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Time Factors
  • Transfection

Substances

  • Albumins
  • Antineoplastic Agents
  • Drug Carriers
  • Imines
  • Magnetite Nanoparticles
  • Polyethylenes
  • Protein Kinase Inhibitors
  • poly(ethylene imine)
  • Interferon-gamma
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab