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

作　　者：马凯伦 谷继伟[2] 颜承云 MA Kailun;GU Jiwei;YAN Chengyun(College of Pharmaty,Guilin Medical University,Guilin 541199,China;The First Affiliated Hospital of Jiamusi University,Jiamusi 154000,China)

机构地区：[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

出　　处：《华夏医学》2024年第2期61-67,共7页Acta Medicinae Sinica

基　　金：国家自然科学基金项目(ZZ165006);广西自然科学基金项目(2022GXNSFDA035085)。

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(NLSKALA-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NLSKALA-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0.01~1000 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。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 NLSKALA-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 0.01-1000 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 

分 类 号：R943[医药卫生—药剂学]