黑色素微粒修饰阿霉素对甲状腺未分化癌细胞耐药性的影响

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摘要目的探究黑色素微粒修饰阿霉素（DOX-MNPs）对甲状腺未分化癌细胞（ATC）耐药性的影响。方法合成多巴胺黑色素纳米粒（MNPs）并加载阿霉素（DOX），紫外-可见光谱法测定不同质量比下MNPs的载药效率和容量，透射电子显微镜（TEM）和Brookhaven Zeta PALS分析仪分析纳米颗粒的特性。不同浓度的游离DOX和DOX-MNPs（0、10、20、40、80、160 mg/L）作用于ATC药物敏感细胞株HTh74和耐药细胞株HTh74R，MTT法检测细胞活力，流式细胞术检测细胞对DOX的摄取能力。结果 DOX-MNPs的负载效率随DOX和MNPs质量比的增加而降低，当质量比为0.167∶1时，加载效果达到峰值93.45%，该质量比下得到的DOX-MNPs具有与MNPs相似的形态，动作电位和粒径分布分别为13.79 mV和（241.1±4.8）nm。在HTh74R细胞中，DOX-MNPs浓度高于20 mg/L时，细胞活力显著低于同等药物浓度游离DOX（P < 0.05），DOX-MNPs的摄取率明显高于游离DOX（P < 0.05），与HTh74细胞的摄取程度相似。结论在耐药HTh74R细胞中，DOX-MNPs的细胞摄取能力和治疗效果显著高于同等药物浓度下的游离DOX。

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	张余春1
	2 张青1 杨昱1 赵一璟1 王昆1 马向华2

关键词 ：甲状腺未分化癌, 耐药性, 阿霉素, 多巴胺黑色素纳米粒

Abstract：Objective To research the influence of Doxorubicin loaded melanin nanoparticles (DOX-MNPs) on drug resistance of anaplastic thyroid cancer (ATC) cells. Methods Dopamine-melanin nanoparticles (MNPs) were synthesized as previously reported and Doxorubicin (DOX) was loaded onto MNPs. The loading efficiency and capacity of MNPs at different mass ratios of DOX to MNPs were determined by UV-Vis spectroscopy and the characterization of nanoparticles was acquired by transmission electron microscopy (TEM) and Brookhaven Zeta PALS analyzer. HTh74 and HTh74R cells were incubated with various concentrations of free DOX and DOX-MNPs (0, 10, 20, 40, 80, 160 mg/L). Cell viability was determined by MTT, and intracellular DOX fluorescent signal was determined by flow cytometry studies. Results The MNPs was successfully synthesized and the loading efficiency of DOX-MNPs decreased with the increasing mass ratio of DOX to MNPs. The loading efficacy peaked at 93.45% when the mass ratio was 0.167:1. At this mass ratio, the obtained DOX-MNPs had similar morphology to MNPs, and zeta potential and size distribution of DOX-MNPs were 13.79 mV and (241.1±4.8) nm. In HTh74R cells, when the concentration of DOX-MNPs was higher than 20 mg/L, the cell viability was significantly lower than that of the equivalent drug concentration (P < 0.05), and the uptake rate of DOX-MNPs was significantly higher than that of free DOX (P < 0.05). The degree of uptake was similar to that of HTh74 cells. Conclusion The cellular uptake capacity and therapeutic effect of the DOX-MNPs are significantly higher than those of free DOX at the same drug concentration in drug-resistant HTh74R cells.

Key words： Anaplastic thyroid carcinoma Drug resistance Doxorubicin Dopamine-melanin nanoparticles

基金资助:国家自然科学基金资助项目（81870542）。

通讯作者: 王昆（1972-），男，博士，副主任医师，硕士生导师；研究方向：内分泌与代谢病；马向华（1962-），男，硕士，主任医师，博士生导师；研究方向：内分泌与代谢病。

作者简介: 张余春（1986-），男，南京医科大学第一临床医学院在读硕士研究生；研究方向：内分泌与代谢病。

引用本文:

张余春1,2 张青1 杨昱1 赵一璟1 王昆1 马向华2. 黑色素微粒修饰阿霉素对甲状腺未分化癌细胞耐药性的影响[J]. 中国医药导报, 2018, 15(29): 4-8.
ZHANG Yuchun1,2 ZHANG Qing1 YANG Yu1 ZHAO Yijing1 WANG Kun1 MA Xianghua2. Research of the influence of Doxorubicin loaded melanin particles on drug resistance of anaplastic thyroid cancer cells. 中国医药导报, 2018, 15(29): 4-8.

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