Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan.
Int J Pharm. 2024 Dec 25;667(Pt A):124856. doi: 10.1016/j.ijpharm.2024.124856. Epub 2024 Oct 24.
To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11. We first co-entrap OMNP and CPT-11 in self-assembled lipid-PLGA NP to prepare OLNP@CPT-11. The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. The OLNP-CET@CPT-11 enables dual targeting through both external magnetic guidance and CET-mediated active targeting. The NP was characterized for physicochemical properties using various analytical techniques. In vitro study confirms ligand-receptor interaction results in enhanced endocytosis of OLNP-CET@CPT-11 by U87 cells, which offers increased cytotoxicity and elevated cell apoptosis rates. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.
为了包载疏水性的药物如 CPT-11（伊立替康），聚（乳酸-共-乙醇酸）（PLGA）纳米粒（NP）因其低细胞毒性和已被批准用于临床而备受青睐。另一方面，将油酸包覆的氧化铁磁性纳米粒子（OMNP）包载于 PLGA NP 中可为磁性靶向药物递送提供纳米载体。我们在本研究中的目标是开发一种新的用于递送 CPT-11 的双靶向磁性脂质-聚合物 NP。我们首先将 OMNP 和 CPT-11 共包载于自组装的脂质-PLGA NP 中以制备 OLNP@CPT-11。OLNP@CPT-11 表面用表皮生长因子受体（EGFR）抗体 Cetuximab（CET）进行修饰，它可以主动靶向 U87 脑胶质瘤细胞表面过表达的 EGFR。OLNP-CET@CPT-11 通过外部磁场引导和 CET 介导的主动靶向实现双重靶向。采用各种分析技术对 NP 的理化性质进行了表征。体外研究证实配体-受体相互作用导致 U87 细胞对 OLNP-CET@CPT-11 的内吞作用增强，从而提高了细胞毒性和细胞凋亡率。此外，OLNP-CET@CPT-11 对 U87 细胞的磁导向作用可仅在磁靶向区域诱导细胞死亡。双靶向策略还为静脉注射 OLNP-CET@CPT-11 治疗裸鼠皮下植入的 U87 肿瘤提供了最佳的治疗效果。
