Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging.

Abstract

The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is demonstrated to be capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd(3+) contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, it is demonstrated that TAT-Au NPs are capable of delivering Gd(3+) chelates for enhanced brain tumor imaging with a prolonged retention time of Gd(3+) when compared to the free Gd(3+) chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.

• Authors: Yu Cheng, Qing Dai, Ramin A Morshed, Xiaobing Fan, Michelle L Wegscheid, Derek A Wainwright, Yu Han, Lingjiao Zhang, Brenda Auffinger, Alex L Tobias, Esther Rincón, Bart Thaci, Atique U Ahmed, Peter C Warnke, Chuan He, Maciej S Lesniak
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 10 Issue 24 Pg. 5137-50 (Dec 29 2014) ISSN: 1613-6829 [Electronic] Germany
• PMID: 25104165 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibiotics, Antineoplastic
• Contrast Media
• Gold
• Doxorubicin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics, therapeutic use)
• Blood-Brain Barrier
• Brain Neoplasms (drug therapy, pathology)
• Contrast Media
• Doxorubicin (administration & dosage, pharmacokinetics, therapeutic use)
• Glioma (drug therapy, pathology)
• Gold (chemistry)
• Magnetic Resonance Imaging
• Metal Nanoparticles
• Mice