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用于鼻咽癌治疗的载顺铂细胞穿透肽修饰磁性纳米颗粒的合成

[Synthesis of cell penetrating peptide decorated magnetic nanoparticles loading cisplatin for nasopharyngeal cancer therapy].

作者信息

Quan L M, Zhong Y, Weng H H

机构信息

1Department of Otorhinolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510000,China.

出版信息

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Jul;32(13):963-968. doi: 10.13201/j.issn.1001-1781.2018.13.001.

DOI:10.13201/j.issn.1001-1781.2018.13.001
PMID:29986554
Abstract

To synthesize cisplatin loaded and cell penetrating peptide TAT decorated magnetic nanoparticles and to observe the inhibiting effect in vitro on nasopharyngeal cancer therapy.The aldehyde sodium alginate coated magnetic nanoparticles (ASA-MNPs) was prepared as the drug delivery system, which was covalently attached by PEGylation TAT (TAT-ASA-MNPs) via condensation of aldehyde with amino group and then coordinated with cisplatin (TAT-ASA-MNPs@CDDP). The complex was characterized by H-NMR and FT-IR. The cell penetrating ability and biocompatibility were observed by means of fluorescent tags. The inhibited effect on nasopharyngeal cancer CNE-2 cells was measured by cellular toxicity research and flow cytometry.The H NMR and FT-IR of TAT-ASA-MNPs exhibited the characteristic peaks of TAT, PEG as well as ASA. The dynamic light scattering showed the hydrodynamic diameter of the complex was(145.9±1.5)nm. Zeta potential was(-21.66±1.24)mV and the drug loading rate was(25.03±3.05)%. Fluorescent labeling assay revealed that FITC marked TATASAMNPs was quickly taken up by CNE-2 cells. Cytotoxicity experiment on 293T cells displayed high survival rate (>70%) after cultured for 72h. Negative hemagglutination reflected decent biocompatibility. In vitro cytotoxicity test and cell apoptosis assay exhibited obvious inhibition on CNE-2 cell with TATASAMNPs@CDDP at low concentration of cisplatin compared to ASA-MNPs@CDDP (<0.05).TAT-ASA-MNPs showed decent biocompatibility while distinctly inhibit CNE-2 cells in vitro study.

摘要

合成负载顺铂并修饰细胞穿透肽TAT的磁性纳米颗粒,并观察其对鼻咽癌治疗的体外抑制作用。制备醛基海藻酸钠包被的磁性纳米颗粒(ASA-MNPs)作为药物递送系统,通过醛基与氨基的缩合将聚乙二醇化TAT(TAT-ASA-MNPs)共价连接到其上,然后与顺铂配位(TAT-ASA-MNPs@CDDP)。通过氢核磁共振(H-NMR)和傅里叶变换红外光谱(FT-IR)对该复合物进行表征。通过荧光标记观察其细胞穿透能力和生物相容性。通过细胞毒性研究和流式细胞术测量对鼻咽癌CNE-2细胞的抑制作用。TAT-ASA-MNPs的H NMR和FT-IR显示出TAT、聚乙二醇(PEG)以及海藻酸钠(ASA)的特征峰。动态光散射显示该复合物的流体动力学直径为(145.9±1.5)nm。zeta电位为(-21.66±1.24)mV,载药率为(25.03±3.05)%。荧光标记试验表明,异硫氰酸荧光素(FITC)标记的TAT-ASA-MNPs能被CNE-2细胞快速摄取。对293T细胞的细胞毒性实验显示,培养72小时后存活率较高(>70%)。阴性血凝反应表明其生物相容性良好。体外细胞毒性试验和细胞凋亡检测显示,与ASA-MNPs@CDDP相比,低浓度顺铂的TAT-ASA-MNPs@CDDP对CNE-2细胞有明显抑制作用(<0.05)。在体外研究中,TAT-ASA-MNPs表现出良好的生物相容性,同时能显著抑制CNE-2细胞。

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