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Publication : Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma.

First Author  Agemy L Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  42 Pages  17450-5
PubMed ID  21969599 Mgi Jnum  J:177445
Mgi Id  MGI:5295114 Doi  10.1073/pnas.1114518108
Citation  Agemy L, et al. (2011) Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. Proc Natl Acad Sci U S A 108(42):17450-5
abstractText  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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