Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 42, Pages 17450-17455Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1114518108
Keywords
angiogenesis; apoptosis; tumor targeting; tumor treatment
Categories
Funding
- National Cancer Institute [CA152327, CA124427]
- Cancer Center [CA30199]
- National Institute of Allergy and Infectious Diseases [R37AI048034]
- Leducq Foundation
- Merieux Foundation
- Ipsen/Biomeasure
- Frances C. Berger Foundation
- European Molecular Biology Organization
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Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and (iii) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.
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