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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

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 Gd3+ 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 Gd3+ chelates for enhanced brain tumor imaging with a prolonged retention time of Gd3+ when compared to the free Gd3+ chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.

Original languageEnglish (US)
Pages (from-to)5137-5150
Number of pages14
JournalSmall
Volume10
Issue number24
DOIs
StatePublished - Dec 29 2014

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)
  • Engineering (miscellaneous)

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