首页|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

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

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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-SS-HA@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。
In vitro research of stimuli-responsive mesoporous silica nanoparticles loaded with anthra-quinone-modified 4S on triple-negative breast cancer
Objective:To investigate whether stimuli-responsive mesoporous silica nanoparticles(MSNs-SS-HA)as a drug delivery system can improve the targeting and bioavailability of anthraquinone-modified 4S to tri-ple-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 analy-sis.In vitro dialysis experiments were performed to detect the release behavior of MSNs@4S and MSNs-SS-HA@4S in different concentrations of glutathione buffer solutions.The inhibitory activity of free 4S and drug-loaded 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 anthra-quinone-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 effi-ciency of(17.43±1.2)％and(90.56±1.1)％,respectively.The drug-loaded nanoparticles MSNs-SS-HA@4S exhib-it 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.Conclu-sion:MSNs-SS-HA@4S improves the efficacy of anthraquinone modified-4S in potentiation and toxicity reduc-tion,providing new ideas for targeted therapy of TNBC.

anthraquinone-modified 4Smesoporous silica nanoparticlesstimulus responsivenesstumor target-ingtriple-negative breast cancer

陈强健、赵英丹、李欣晓、许淑妹、杨盈盈、侯华新、黎丹戎

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广西医科大学生命科学研究院,南宁 530021

广西医科大学肿瘤医学院,南宁 530021

广西医科大学药学院,南宁 530021

蒽醌修饰物4S 介孔二氧化硅纳米粒 刺激响应性 肿瘤靶向 三阴性乳腺癌

国家自然科学基金资助项目广西自然科学基金重点项目区域性高发肿瘤早期防治研究教育部重点实验室自主课题

822607142020GXNSFDA238016GKE-ZZ202237

2024

10.16190/j.cnki.45-1211/r.2024.06.002

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子：0.788
ISSN：1005-930X
年,卷(期)：2024.41(6)