title: 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.affiliation: The Brain Tumor Center, The University of Chicago , Chicago, Illinois United States.
authors.forename: Ramin A
authors.initials: RA
authors.lastname: Morshed
authors.affiliation: Northwestern University Feinberg School of Medicine , 676 North Saint Clair Street, Suite 2210, Chicago, Illinois 60611, United States.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Muroski
authors.affiliation: Department of Chemistry, Institute of Biophysics Dynamics and Howard Hughes Medical Institute, The University of Chicago , Chicago, Illinois United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.affiliation: The Brain Tumor Center, The University of Chicago , Chicago, Illinois United States.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wegscheid
authors.affiliation: The Brain Tumor Center, The University of Chicago , Chicago, Illinois United States.
authors.forename: Brenda
authors.initials: B
authors.lastname: Auffinger
authors.affiliation: Northwestern University Feinberg School of Medicine , 676 North Saint Clair Street, Suite 2210, Chicago, Illinois 60611, United States.
authors.forename: Dou
authors.initials: D
authors.lastname: Yu
authors.affiliation: Northwestern University Feinberg School of Medicine , 676 North Saint Clair Street, Suite 2210, Chicago, Illinois 60611, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: The Brain Tumor Center, The University of Chicago , Chicago, Illinois United States.
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Northwestern University Feinberg School of Medicine , 676 North Saint Clair Street, Suite 2210, Chicago, Illinois 60611, United States.
authors.forename: Meijing
authors.initials: M
authors.lastname: Wu
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Northwestern University Feinberg School of Medicine , 676 North Saint Clair Street, Suite 2210, Chicago, Illinois 60611, United States.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude
chemical_list: D057846:Cell-Penetrating Peptides; D006046:Gold; D004317:Doxorubicin; D053148:Caspase 3
keywords: brain metastatic breast cancer; chemotherapeutics; drug delivery; metastatic microsatellites; nanoparticles