Quan L M, Zhong Y, Weng H H
1Department of Otorhinolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510000,China.
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.
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 TATASAMNPs 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 TATASAMNPs@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.
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。