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

文献索引：Small 10(24) , 5137-50, (2014)

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摘要

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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.