Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

Lilach Agemy, Dinorah Friedmann-Morvinski, Venkata Ramana Kotamraju, Lise Roth, Kazuki N. Sugahara, Olivier M. Girard, Robert F. Mattrey, Inder M. Verma, Erkki Ruoslahti

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

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 tumorhoming 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.

Original languageEnglish (US)
Pages (from-to)17450-17455
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number42
DOIs
StatePublished - Oct 18 2011

Keywords

  • Angiogenesis
  • Apoptosis
  • Tumor targeting
  • Tumor treatment

ASJC Scopus subject areas

  • General

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  • Cite this

    Agemy, L., Friedmann-Morvinski, D., Kotamraju, V. R., Roth, L., Sugahara, K. N., Girard, O. M., Mattrey, R. F., Verma, I. M., & Ruoslahti, E. (2011). Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. Proceedings of the National Academy of Sciences of the United States of America, 108(42), 17450-17455. https://doi.org/10.1073/pnas.1114518108