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Journal Article
Research Support, Non-U.S. Gov't
Pep-1&borneol-Bifunctionalized Carmustine-Loaded Micelles Enhance Anti-Glioma Efficacy Through Tumor-Targeting and BBB-Penetrating.
Journal of Pharmaceutical Sciences 2019 May
Tumor-targeting and blood-brain barrier (BBB)-penetrating are highly desirable for the treatment of glioma. In this study, we developed Pep-1&borneol-bifunctionalized carmustine-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting interleukin-13 receptor-overexpressed glioma and penetrating the brain microvascular endothelial cells-associated physiologic barriers. Pep-1/Bor/CMS-M were nearly spherical particles with a diameter of 32.6 ± 1.1 nm and zeta potential of -21.3 ± 3.1 mV. Carmustine (CMS) released from Pep-1/Bor/CMS-M in pH 7.4 was significantly faster than in acidic environments. In human glioma BT325 cellular studies, Pep-1/Bor/CMS-M remarkably increased the cytotoxicity, notably improved the internalization, and effectively induced the cell apoptosis. Likewise, in human brain microvascular endothelial cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance, and thereby enhanced the ability of penetration. In orthotopic Luc-BT325 glioma tumor-bearing nude mouse models, the stronger fluorescence signal and longer retention were observed in brain tissues compared with other controls, after single administration of DiD-labeled Pep-1/Bor/M (DiD/Pep-1/Bor/M). Importantly, Pep-1/Bor/CMS-M displayed the strongest inhibition of tumor growth, the longest survival period, and low systemic toxicity in treating orthotopic glioma tumor-bearing nude mice. Simultaneous functionalization of Pep-1 and borneol offers a novel strategy for designing CMS-based nanomedicine and precisely treating glioma.
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