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

202 Citations (Scopus)

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

Fingerprint

Glioblastoma
Nanoparticles
Peptides
Neoplasms
Therapeutics
Mitochondria
Therapeutic Uses
Endothelial Cells
Survival

Keywords

  • Angiogenesis
  • Apoptosis
  • Tumor targeting
  • Tumor treatment

ASJC Scopus subject areas

  • General

Cite this

Agemy, L., Friedmann-Morvinski, D., Kotamraju, V. R., Roth, L., Sugahara, K. N., Girard, O. 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

Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. / Agemy, Lilach; Friedmann-Morvinski, Dinorah; Kotamraju, Venkata Ramana; Roth, Lise; Sugahara, Kazuki N.; Girard, Olivier M.; Mattrey, Robert F.; Verma, Inder M.; Ruoslahti, Erkki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 42, 18.10.2011, p. 17450-17455.

Research output: Contribution to journalArticle

Agemy, L, Friedmann-Morvinski, D, Kotamraju, VR, Roth, L, Sugahara, KN, Girard, OM, Mattrey, RF, Verma, IM & 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, vol. 108, no. 42, pp. 17450-17455. https://doi.org/10.1073/pnas.1114518108
Agemy, Lilach ; Friedmann-Morvinski, Dinorah ; Kotamraju, Venkata Ramana ; Roth, Lise ; Sugahara, Kazuki N. ; Girard, Olivier M. ; Mattrey, Robert F. ; Verma, Inder M. ; Ruoslahti, Erkki. / Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 42. pp. 17450-17455.
@article{6082a7ad0b914f4aad5d43535708c832,
title = "Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma",
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.",
keywords = "Angiogenesis, Apoptosis, Tumor targeting, Tumor treatment",
author = "Lilach Agemy and Dinorah Friedmann-Morvinski and Kotamraju, {Venkata Ramana} and Lise Roth and Sugahara, {Kazuki N.} and Girard, {Olivier M.} and Mattrey, {Robert F.} and Verma, {Inder M.} and Erkki Ruoslahti",
year = "2011",
month = "10",
day = "18",
doi = "10.1073/pnas.1114518108",
language = "English (US)",
volume = "108",
pages = "17450--17455",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "42",

}

TY - JOUR

T1 - Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma

AU - Agemy, Lilach

AU - Friedmann-Morvinski, Dinorah

AU - Kotamraju, Venkata Ramana

AU - Roth, Lise

AU - Sugahara, Kazuki N.

AU - Girard, Olivier M.

AU - Mattrey, Robert F.

AU - Verma, Inder M.

AU - Ruoslahti, Erkki

PY - 2011/10/18

Y1 - 2011/10/18

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Apoptosis

KW - Tumor targeting

KW - Tumor treatment

UR - http://www.scopus.com/inward/record.url?scp=80054795004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054795004&partnerID=8YFLogxK

U2 - 10.1073/pnas.1114518108

DO - 10.1073/pnas.1114518108

M3 - Article

C2 - 21969599

AN - SCOPUS:80054795004

VL - 108

SP - 17450

EP - 17455

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 42

ER -