SP94与BR2配体共修饰双载苦参衍生物B21-DOX脂质体的制备及其体外抗肝癌作用
Preparation of double-loaded bitter ginseng derivative B21-DOX liposomes co-modified with SP94 and BR2 ligand and its in vitro anti-hepatocarcinogenic effect.
发表日期:2024 Aug 16
作者:
Lin Jing, Jiajia Zhang, Lili Li, Simei Luo, Zijun Tang, Xu Liu, Yonglong Zhong, Mingqing Yuan
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
构建SP94和BR2配体共修饰的新型脂质体药物递送系统,封装苦参衍生物B21和阿霉素(DOX),以实现优异的抗肿瘤功效并降低毒副作用。采用有机相制备脂质体反应方法,B21 封装在脂相中,DOX 封装在水相中。脂质体进一步用 SP94 和 BR2 肽修饰。通过紫外分光光度法、高效液相色谱、纳米尺寸分析、超滤离心、透析、透射电子显微镜、流式细胞术、甲基噻唑基二苯基四唑溴化物测定、共聚焦激光等方法评估表征、细胞毒性和体外靶向效果SP94/BR2-B21/DOX-LP脂质体呈球形,平均直径为120.87±1.00nm,多分散指数(PDI)为0.223±0.006,表面电荷为-23.1 ± 1.27 mV。 B21 和 DOX 的包封率分别大于 85% 和 97% (mg/mg)。结果表明,与单配体修饰和未修饰的脂质体相比,SP94/BR2-B21/DOX-LP表现出增强的靶向性和细胞毒性,并且B21和DOX的联合封装显示出协同抗肝癌作用。SP94/BR2-B21/DOX -LP脂质体代表了一种有前景的肝细胞癌靶向药物递送系统,可改善膜渗透性、增强治疗效果并降低全身毒性。
To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects.Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay.SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of -23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects.SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.