Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods

Biomaterials. 2014 Sep;35(29):8374-84. doi: 10.1016/j.biomaterials.2014.05.094. Epub 2014 Jul 1.

Abstract

Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention of GNR@DOX nanoparticles were attributed to their abilities to induce cellular apoptosis/necrosis and ablate intratumoral blood vessels. All these results suggested a considerable potential of GNR@DOX nanoplatform for treatment of metastatic breast cancer.

Keywords: Chemotherapy; Doxorubicin; Gold nanorods; Metastatic breast cancer; Photothermal ablation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use*
  • Breast / drug effects
  • Breast / pathology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • DNA Adducts / administration & dosage
  • DNA Adducts / therapeutic use*
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use*
  • Female
  • Gold / chemistry
  • Gold / therapeutic use*
  • Humans
  • Hyperthermia, Induced
  • Lung / drug effects
  • Lung / pathology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Phototherapy

Substances

  • Antibiotics, Antineoplastic
  • DNA Adducts
  • doxorubicin-DNA
  • Gold
  • Doxorubicin