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Blood‐Brain Barrier Permeable Gold Nanoparticles: An Efficient Delivery Platform for Enhanced Malignant Glioma Therapy and Imaging

2014; Wiley; Volume: 10; Issue: 24 Linguagem: Inglês

10.1002/smll.201400654

1613-6829

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 Thaçi, Atique U. Ahmed, Peter C. Warnke, Chuan He, Maciej S. Lesniak,

Nanoparticle-Based Drug Delivery

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.