刺激响应型MSNs负载蒽醌修饰物4S对三阴性乳腺癌的体外研究

In vitro research of stimuli-responsive mesoporous silica nanoparticles loaded with anthraquinone-modified 4S on triple-negative breast cancer

目的:探讨刺激响应型介孔二氧化硅纳米粒(MSNs-SS-HA)作为药物递送系统是否能提高蒽醌修饰物4S对三阴性乳腺癌(TNBC)细胞的靶向性、生物利用度,并降低对正常细胞的毒性。方法:后修饰法制备功能化的纳米粒MSNs-SS-HA,利用透射电镜、马尔文粒径仪、傅里叶红外光谱和元素分析等对纳米粒进行表征。体外透析实验检测MSNs@4S和MSNs-SSHA@4S在不同浓度的谷胱甘肽缓冲溶液中的释放行为。MTT试验测定游离4S和载药纳米粒对TNBC细胞MDA-MB231、乳腺癌细胞MCF-7和乳腺正常细胞MCF-10A的抑制活性。激光共聚焦显微镜观察蒽醌修饰物4S和载药纳米粒在不同细胞中的摄取情况。结果:成功制备功能化的载药纳米粒MSNs-SS-HA@4S,其载药量和包封率分别为(17.43±1.2)%和(90.56±1.1)%。载药纳米粒MSNs-SS-HA@4S具有还原响应特性,同时具有缓控释药作用。在相同浓度下,MSNs-SS-HA@4S对MDA-MB231细胞的毒性高于MCF-10A细胞,而对MCF-7细胞的抗肿瘤活性较弱(P<0.05)。体外细胞摄取实验表明,MSNs-SS-HA@4S能够靶向CD44受体高表达的TNBC细胞MDA-MB231,可能通过CD44受体介导的内吞作用进入细胞,揭示了MSNs-SS-HA@4S具有肿瘤靶向治疗潜能。结论:MSNs-SS-HA@4S提高了蒽醌修饰物4S增效减毒的功效,为TNBC的靶向治疗提供新思路。

Objective:To investigate whether stimuli-responsive mesoporous silica nanoparticles(MSNs-SSHA)as a drug delivery system can improve the targeting and bioavailability of anthraquinone-modified 4S to triple-negative breast cancer(TNBC)cells,while minimizing the toxicity to normal cells.Methods:Functionalized nanoparticles MSNs-SS-HA were prepared by post-modification method,and characterized through transmission electron microscopy,Malvern particle size analyzer,Fourier transform infrared spectroscopy,and elemental analysis.In vitro dialysis experiments were performed to detect the release behavior of MSNs@4S and MSNs-SSHA@4S in different concentrations of glutathione buffer solutions.The inhibitory activity of free 4S and drugloaded nanoparticles on TNBC cells MDA-MB231,breast cancer cells MCF-7 and normal breast cancer cells MCF-10A was determined by MTT assay.Laser confocal microscopy was used to observe the uptake of anthraquinone-modified 4S and drug-loaded nanoparticles in different cells.Results:Functionalized drug-loaded nanoparticles MSNs-SS-HA@4S were successfully prepared,with a drug loading capacity and encapsulation efficiency of(17.43±1.2)%and(90.56±1.1)%,respectively.The drug-loaded nanoparticles MSNs-SS-HA@4S exhibit reduction-responsive properties and slow-release drug effects.At the same concentration,the toxicity of MSNs-SS-HA@4S to MDA-MB231 cells was higher than that to MCF-10A cells,but the antitumor activity against MCF-7 cells was weaker(P<0.05).In vitro cellular uptake experiments showed that MSNs-SS-HA@4S was able to target MDA-MB231,a TNBC cell with high expression of CD44,and might enter the cells through CD44 receptor-mediated endocytosis,revealing the potential of MSNs-SS-HA@4S for tumor-targeted therapy.Conclusion:MSNs-SS-HA@4S improves the efficacy of anthraquinone modified-4S in potentiation and toxicity reduction,providing new ideas for targeted therapy of TNBC.