Enhanced Glioblastoma Targeting Ability of Carfilzomib Enabled by a DA7R-Modified Lipid Nanodisk
| Autor: | Huan Wang, Mingfei Zhang, Jun Pan, Zhilan Chai, Weiyue Lu, Changyou Zhan, Songli Wang, Linwei Lu, Man Ying, Huitong Ruan, Xiaoyi Wang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Chemistry Pharmaceutical Science Peptide Kinase insert domain receptor medicine.disease Carfilzomib In vitro 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine In vivo 030220 oncology & carcinogenesis Glioma Drug Discovery Cancer cell medicine Cancer research Molecular Medicine Glioblastoma |
| Zdroj: | Molecular Pharmaceutics. 15:2437-2447 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.8b00270 |
| Popis: | The robust proliferation of tumors relies on a rich neovasculature for nutrient supplies. Therefore, a basic strategy of tumor targeting therapy should include not only killing regular cancer cells but also blocking tumor neovasculature. D-peptide DA7R, which was previously reported to specifically bind vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), could achieve the goal of multitarget recognition. Accordingly, the main purposes of this work were to establish a carfilzomib-loaded lipid nanodisk modified with multifunctional peptide DA7R (DA7R-ND/CFZ) and to evaluate its anti-glioblastoma efficacy in vitro and in vivo. It is testified that the DA7R peptide-conjugated lipid nanodisk can be specifically taken up by U87MG cells and HUVECs. Furthermore, DA7R-ND demonstrated a more enhanced penetration than that of the nonmodified formulation on the tumor spheroid model in vitro and more tumor region accumulation in vivo on the subcutaneous and intracranial tumor-bearing nude ... |
| Databáze: | OpenAIRE |
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