Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer

Ramin A. Morshed, Megan E. Muroski, Qing Dai, Michelle L. Wegscheid, Brenda Auffinger, Dou Yu, Yu Han, Lingjiao Zhang, Meijing Wu, Yu Cheng*, Maciej S. Lesniak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

As therapies continue to increase the lifespan of patients with breast cancer, the incidence of brain metastases has steadily increased, affecting a significant number of patients with metastatic disease. However, a major barrier toward treating these lesions is the inability of therapeutics to penetrate into the central nervous system and accumulate within intracranial tumor sites. In this study, we designed a cell-penetrating gold nanoparticle platform to increase drug delivery to brain metastatic breast cancer cells. TAT peptide-modified gold nanoparticles carrying doxorubicin led to improved cytotoxicity toward two brain metastatic breast cancer cell lines with a decrease in the IC50 of at least 80% compared to free drug. Intravenous administration of these particles led to extensive accumulation of particles throughout diffuse intracranial metastatic microsatellites with cleaved caspase-3 activity corresponding to tumor foci. Furthermore, intratumoral administration of these particles improved survival in an intracranial MDA-MB-231-Br xenograft mouse model. Our results demonstrate the promising application of gold nanoparticles for improving drug delivery in the context of brain metastatic breast cancer.

Original languageEnglish (US)
Pages (from-to)1843-1854
Number of pages12
JournalMolecular Pharmaceutics
Volume13
Issue number6
DOIs
StatePublished - Jun 6 2016

Keywords

  • brain metastatic breast cancer
  • chemotherapeutics
  • drug delivery
  • metastatic microsatellites
  • nanoparticles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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