Preprint Article Version 1 This version is not peer-reviewed

Pep-1&Borneol-Bifunctionalized Carmustin-Loaded Micelles Enhance Anti-Glioma Efficacy through Tumor Targeting and BBB Penetrating

Version 1 : Received: 23 October 2018 / Approved: 24 October 2018 / Online: 24 October 2018 (11:53:00 CEST)

How to cite: Guo, X.; Wu, G.; Qin, Y.; Wang, H.; Qu, D.; Chen, L. Pep-1&Borneol-Bifunctionalized Carmustin-Loaded Micelles Enhance Anti-Glioma Efficacy through Tumor Targeting and BBB Penetrating. Preprints 2018, 2018100574 (doi: 10.20944/preprints201810.0574.v1). Guo, X.; Wu, G.; Qin, Y.; Wang, H.; Qu, D.; Chen, L. Pep-1&Borneol-Bifunctionalized Carmustin-Loaded Micelles Enhance Anti-Glioma Efficacy through Tumor Targeting and BBB Penetrating. Preprints 2018, 2018100574 (doi: 10.20944/preprints201810.0574.v1).

Abstract

Abstract: 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 carmustin-loaded micelles (Pep-1/Bor/CMS-M) capable of targeting to IL-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 dimeter 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 (HBMEC) cells, Pep-1/Bor/CMS-M obviously promoted the cellular uptake, rapidly decreased the transepithelial electrical resistance (TEER) and thereby of enhancing 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-labelled 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.

Subject Areas

carmustine-loaded micelle; brain targeting; borneol; IL-13 receptor; BBB

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