On-command drug release from nanochains inhibits growth of breast tumors

Pharm Res. 2014 Jun;31(6):1460-8. doi: 10.1007/s11095-013-1102-8. Epub 2013 Aug 9.

Abstract

Purpose: To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor.

Methods: A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the 4T1-LUC-GFP orthotopic mouse model, which is a highly aggressive breast cancer model. The 4T1-LUC-GFP cell line stably expresses firefly luciferase, which allowed the non-invasive in vivo imaging of tumor response to the treatment using bioluminescence imaging (BLI).

Results: Longitudinal BLI imaging showed that a single nanochain treatment followed by application of RF resulted in an at least 100-fold lower BLI signal compared to the groups treated with nanochains (without RF) or free doxorubicin followed by RF. A statistically significant increase in survival time of the nanochain-treated animals followed by RF (64.3 days) was observed when compared to the nanochain-treated group without RF (35.7 days), free doxorubicin-treated group followed by RF (38.5 days), and the untreated group (30.5 days; n=5 animals per group).

Conclusions: These studies showed that the combination of RF and nanochains has the potential to effectively treat highly aggressive cancers and prolong survival.

Publication types

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

MeSH terms

  • Adjuvants, Pharmaceutic
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Luminescence
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use
  • Radio Waves
  • Survival Analysis
  • Tumor Burden

Substances

  • Adjuvants, Pharmaceutic
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin