Enhanced efficacy of combined temozolomide and bromodomain inhibitor therapy for gliomas using targeted nanoparticles
Name
s41467-018-04315-4.pdf
Size
2.5 MB
Format
Adobe PDF
Checksum (MD5)
86b87caba981ed5f56a2e5f183ac1544
Author(s)
Vu Han, Tu-Lan
Balkanska-Sinclair, Elena
Floyd, Scott R
Lam, Fred Chiu-Lai
Morton, Stephen Winford
Wyckoff, Jeffrey
Vu-Han, Tu-Lan
Hwang, Mun Kyung
Maffa, Amanda
Yaffe, Michael B
Date Issued
May 2018
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Lam, Fred C. et al. “Enhanced Efficacy of Combined Temozolomide and Bromodomain Inhibitor Therapy for Gliomas Using Targeted Nanoparticles.” Nature Communications 9, 1 (May 2018): 1991 © 2018 The Author(s)
Version
Final published version
Abstract
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1.5-to 2-fold decrease in tumor burden and corresponding increase in survival compared to equivalent free-drug dosing. Immunocompetent mice treated with Tf-NP-loaded drugs also show protection from the effects of systemic drug toxicity, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to gliomas and other central nervous system tumors.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41467-018-04315-4
