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

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.

• Authors: 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
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 13 Issue 6 Pg. 1843-54 (06 06 2016) ISSN: 1543-8392 [Electronic] United States
• PMID: 27169484 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Cell-Penetrating Peptides
• Gold
• Doxorubicin
• Caspase 3

Topics

• Animals
• Brain (drug effects, metabolism, pathology)
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cell-Penetrating Peptides (administration & dosage, chemistry)
• Doxorubicin (administration & dosage, chemistry)
• Drug Delivery Systems (methods)
• Female
• Gold (chemistry)
• Humans
• Metal Nanoparticles (administration & dosage, chemistry)
• Mice
• Mice, Nude