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透明质酸修饰的载大黄素多壁碳纳米管递药系统的制备及对乳腺癌细胞的抑制作用研究
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| 篇名： | 透明质酸修饰的载大黄素多壁碳纳米管递药系统的制备及对乳腺癌细胞的抑制作用研究 |
| TITLE： | Preparation of HA-modified emodin-contained multi-walled carbon nanotubes drug delivery system and its inhi-bitory effect on breast cancer cells |
| 摘要： | 目的 制备透明质酸（HA）修饰的负载大黄素（EMD）的多壁碳纳米管（MWCNTs）递药系统（HA-MWCNTs-EMD），并研究其对乳腺癌细胞的体外抑制作用。方法将EMD负载于MWCNTs，制得递药系统MWCNTs-EMD；进一步以HA进行修饰，制得递药系统HA-MWCNTs-EMD；对上述两种递药系统进行表征。以游离EMD为参照，考察上述两种递药系统的体外释药情况，检测两种乳腺癌细胞（MCF-7、MDA-MB-231细胞）对系统中EMD的摄取情况，并检测两种递药系统对两种乳腺癌细胞表面糖蛋白分化群44（CD44）表达、活力、凋亡、乳酸脱氢酶（LDH）释放量的影响。结果MWCNTs-EMD、HA-MWCNTs-EMD的包封率均为（63.52±2.74）%，载药量分别为（25.01±1.83）%、（12.13±1.96）%，粒径分别为（865.95±2.16）、（351.86±1.68）nm，多分散性指数分别为0.54±0.02、0.23±0.01，Zeta电位分别为（23.87±0.14）、（－42.79±0.39）mV。MWCNTs-EMD、HA-MWCNTs-EMD在2、4、6、8、10、12、24h时的EMD累积释放量均显著低于同期游离EMD，而HA-MWCNTs-EMD显著高于同期MWCNTs-EMD（P＜0.05）；两种乳腺癌细胞对MWCNTs-EMD、HA-MWCNTs-EMD中EMD的摄取量均显著高于其对游离EMD的摄取量（P＜0.05）；与游离EMD组比较，MWCNTs-EMD、HA-MWCNTs-EMD组两种细胞的凋亡率、LDH释放量均显著升高，表面CD44的表达（MWCNTs-EMD组除外）、细胞活力均显著下调或降低，且HA-MWCNTs-EMD的作用更显著（P＜0.05）。结论成功制备负载EMD的新型递药系统HA-MWCNTs-EMD；该递药系统具有一定的缓释作用，可明显降低乳腺癌细胞活力，促进其凋亡并增加LDH释放，且上述抗乳腺癌作用明显强于游离EMD和MWCNTs-EMD。 |
| ABSTRACT： | OBJECTIVE To prepare hyaluronic acid （HA）-modified emodin （EMD）-contained multi-walled carbon nanotubes （MWCNTs） drug delivery system （HA-MWCNTs-EMD） and explore its in vitro inhibitory effect on breast cancer cells. METHODS EMD was loaded onto MWCNTs to prepare a drug delivery system MWCNTs-EMD； subsequently， the system was further modified with HA to obtain the drug delivery system HA-MWCNTs-EMD. The two drug delivery systems mentioned above were characterized. With free EMD as the reference， the drug release in vitro of the above two drug delivery systems was investigated； the uptake of EMD by two breast cancer cells （MCF-7， MDA-MB-231 cells） was detected. The impacts of the above two drug delivery systems on the expression of surface glycoprotein differentiation group 44 （CD44）， activity， apoptosis and lactate dehydrogenase （LDH） release of two breast cancer cells were detected. RESULTS The encapsulation efficiencies of MWCNTs-EMD and HA-MWCNTs-EMD were both （63.52±2.74）%， with drug loading rates of （25.01±1.83）% and （12.13± 1.96）%， particle sizes of （865.95±2.16） and （351.86±1.68） nm， polydispersity indexes of 0.54±0.02 and 0.23±0.01， and Zeta potentials of （23.87±0.14） and （－42.79±0.39） mV， respectively. The 2， 4， 6， 8， 10， 12 and 24-hour cumulative release rates of EMD in MWCNTs-EMD and HA-MWCNTs-EMD were significantly lower than those in free EMD， while the cumulative release rate of HA-MWCNTs-EMD was significantly higher than that of MWCNTs-EMD （P＜0.05）； the EMD uptakes of MWCNTs-EMD and HA-MWCNTs-EMD by the two types of breast cancer cells were significantly higher than their uptake of free EMD （P＜0.05）. Compared with the free EMD group， the MWCNTs-EMD and MWCNTs-EMD groups showed significantly higher apoptosis rate and LDH release， significantly lower surface CD44 expression （except for the MWCNTs-EMD group） and cell viability in both cell types， and the effect of HA-MWCNTs-EMD was more pronounced （P＜0.05）. CONCLUSIONS A novel drug delivery system HA-MWCNTs- EMD loaded with EMD is developed successfully； the drug delivery system has a certain slow-release effect， which can significantly reduce the activity of breast cancer cells， promote their apoptosis and increase the release of LDH， and the above anti- breast cancer effect is significantly stronger than that of free EMD and MWCNTs-EMD. |
| 期刊： | 2025年第36卷第12期 |
| 作者： | 李瑜多；杜娟；刘云龙；耿峰；陈小兵 |
| AUTHORS： | LI Yuduo，DU Juan，LIU Yunlong，GENG Feng，CHEN Xiaobing |
| 关键字： | 大黄素；多壁碳纳米管；透明质酸；递药系统；乳腺癌；抑制作用 |
| KEYWORDS： | emodin； multi-walled carbon nanotubes； hyaluronic acid； drug delivery system； breast cancer； inhibitory effect |
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