期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-04315-4
关键词
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资金
- Koch Institute Frontier Research Program
- Koch Institute Quinquennial Cancer Research Fellowship
- Bridge Project
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center
- NSF
- Deutscher Akademischer Austusch Dienst (German Academic Exchange Service)
- Koch Institute Frontier Award
- NIH [R01-ES015339, R35-ES028374]
- STARR Consortium grant
- Charles and Marjorie Holloway Foundation
- Koch Institute Clinical Investigator Award
- Burroughs Wellcome Career Award for Medical Scientists
- Marble Center for Nanomedicine at MIT
- Koch Institute Support (core) Grant from the National Cancer Institute [P30-CA14051]
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.
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