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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background: Glioblastoma is the most lethal primary brain malignancy in adults. Standard of care treatment, consisting of temozolomide (TMZ) and adjuvant radiotherapy (RT), mostly does not prevent local recurrence. The inability of drugs to enter the brain, in particular antibody-based drugs and radiosensitizers, is a crucial limitation to effective glioblastoma therapy. Methods: Here, we developed a combined strategy using radiosensitizer gold nanoparticles coated with insulin to cross the blood–brain barrier and shuttle tumor-targeting antibodies (cetuximab) into the brain. Results: Following intravenous injection to an orthotopic glioblastoma mouse model, the nanoparticles specifically accumulated within the tumor. Combining targeted nanoparticle injection with TMZ and RT standard of care significantly inhibited tumor growth and extended survival, as compared to standard of care alone. Histological analysis of tumors showed that the combined treatment eradicated tumor cells, and decreased tumor vascularization, proliferation, and repair. Conclusions: Our findings demonstrate radiosensitizer nanoparticles that effectively deliver antibodies into the brain, target the tumor, and effectively improve standard of care treatment outcome in glioblastoma.

Details

Title
Antibody Delivery into the Brain by Radiosensitizer Nanoparticles for Targeted Glioblastoma Therapy
Author
Gal, Omer 1   VIAFID ORCID Logo  ; Betzer, Oshra 2 ; Rousso-Noori, Liat 3 ; Sadan, Tamar 2 ; Motiei, Menachem 2 ; Nikitin, Maxim 4 ; Friedmann-Morvinski, Dinorah 5   VIAFID ORCID Logo  ; Popovtzer, Rachela 2 ; Popovtzer, Aron 6 

 Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva 4941492, Israel 
 Faculty of Engineering, Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel 
 School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel 
 Moscow Institute of Physics and Technology, MIPT, Dolgoprudny, 141701 Moscow, Russia; Department of Nanobiomedicine, Sirius University of Science and Technology, 354340 Sochi, Russia 
 School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 6997801, Israel 
 Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem 91120, Israel 
First page
177
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
2624845X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2756721834
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.