NLS-KALA-SA纳米粒的制备及细胞核靶向性评价
Preparation of NLS-KALA-SA nanoparticles and evaluation of their nuclear targeting properties
马凯伦 1谷继伟 2颜承云1
作者信息
- 1. 桂林医学院药学院,桂林 541199
- 2. 佳木斯大学附属第一医院,佳木斯 154000
- 折叠
摘要
目的 构建由融合肽KALA、硬脂酸(SA)、核定位信号(NLS)组成的细胞核靶向多肽纳米载体(NLS-KALA-SA,NKSN).方法 采用 Fmoc 多肽固相合成法人工合成 NLS-KALA-SA 多肽纳米载体.结果 NLS-KALA-SA纳米颗粒呈球形,平均尺寸为(76.4±7.6)mm,Zeta电位为(43.7±5.8)mV.纳米颗粒呈正态分布,粒径分布较窄,多分散度指数(PI<0.3).细胞摄取实验研究表明,包载香豆素-6(C-6)的NLS-KALA-SA纳米粒子(C-6/NKSN)主要积聚在 A549 细胞的细胞核中.细胞毒性实验研究表明,在检测浓度为 0.01～1 000 mg/mL时,NLS-KALA-SA对A549 细胞几乎没有细胞毒性.结论 NLS-KALA-SA是一种安全无毒且具有跨膜转运和核定位功能的纳米载体,有望成为一种有前景的癌症治疗多肽纳米载体.
Abstract
Objective To construct a nucleus-targeted nanocarrier(NLS-KALA-SA,NKSN)consisting of fusion peptide KALA,nuclear localization signal(NLS)and stearic acid(SA).Methods The polypeptide nanocarrier NLS-KALA-SA was synthesized by Fmoc solid phase synthesis method.Results The NLS-KALA-SA nanoparticles were spherical shaped with an average size of(76.4±7.6)mm and a Zeta potential of(43.7±5.8)mV.The diameter of nanoparticles follows a normal distribution,with a narrow particle size distribution and a polydispersity index(PI)(PI<0.3).The results of cellular uptake study showed that NLS-KALA-SA nanoparticle loaded with coumarin-6(C6)(C6/NKSN)was predominantly accumulated in the nucleus of A549 cells.The results of cellular toxicity experiments showed that NLS-KALA-SA was almost no cytotoxic to A549 cells at all tested concentrations range of 0.01-1 000 mg/mL.Conclusion The results demonstrate that the NLS-KALA-SA is safe and non-toxic nanocarrier with transmembrane transport and nuclear localization functions,which is expected to become a promising peptide nanocarrier for cancer treatment.
关键词
核定位信号/KAlA肽/纳米粒/核靶向/肺癌Key words
nuclear localization signal/KALA peptide/nanoparticles/nucleus-targeted/lung cancer引用本文复制引用
基金项目
国家自然科学基金(ZZ165006)
广西自然科学基金(2022GXNSFDA035085)
出版年
2024
NETL
NSTL
万方数据