title: 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.affiliation: The Brain Tumor Center, The University of Chicago, MC 3026, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Ramin A
authors.initials: RA
authors.lastname: Morshed
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Fan
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Wegscheid
authors.forename: Derek A
authors.initials: DA
authors.lastname: Wainwright
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Zhang
authors.forename: Brenda
authors.initials: B
authors.lastname: Auffinger
authors.forename: Alex L
authors.initials: AL
authors.lastname: Tobias
authors.forename: Esther
authors.initials: E
authors.lastname: Rincón
authors.forename: Bart
authors.initials: B
authors.lastname: Thaci
authors.forename: Atique U
authors.initials: AU
authors.lastname: Ahmed
authors.forename: Peter C
authors.initials: PC
authors.lastname: Warnke
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006046:Gold / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles; D051379:Mice
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D006046:Gold; D004317:Doxorubicin
keywords: TAT peptide; blood-brain barrier; brain cancer; doxorubicin; gadolinium; gold nanoparticles; malignant glioma
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