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

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• 作者：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
• 刊名：Molecular Pharmaceutics
• 出版年：2016
• 出版时间：June 6, 2016
• 年：2016
• 卷：13
• 期：6
• 页码：1843-1854
• 全文大小：624K
• 年卷期：0
• ISSN：1543-8392

文摘

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.