共载紫杉醇与白藜芦醇靶向纳米粒逆转肿瘤多药耐药性机制及效果研究  

Mechanism and Activity of Reversing Multidrug Resistance by Paclitaxel and Resveratrol Co-Loaded Targeting Nanoparticles

作　　者：陈聪慧 纪雅文 CHEN Conghui;JI Yawen(Medical School,Linyi University,Linyi 276000,China)

机构地区：[1]临沂大学医学院,山东临沂276000

出　　处：《中国药学杂志》2023年第22期2079-2084,共6页Chinese Pharmaceutical Journal

基　　金：山东省自然科学基金青年项目资助(ZR2020QH325);大学生创新创业训练项目资助(X202210452054)。

摘　　要：目的研究制备的共载紫杉醇(paclitaxel,PTX)及白藜芦醇(resveratrol,Rev)靶向纳米粒(FB-nano/PTX-Rev),逆转肿瘤多药耐药性的机制与效果。方法通过对活/死细胞染色,考察联合载药纳米粒体外逆转肿瘤多药耐药性;对用药后耐药细胞中P-gp水平进行测定,考察逆转肿瘤多药耐药的机制;对载药纳米粒进行荷瘤裸鼠的体内抗肿瘤研究,考察其体内安全性及逆转肿瘤多药耐药效果。结果通过对活/死细胞染色分析,FB-nano/PTX-Rev组显示出大面积的死亡耐药细胞,表明可有效杀死耐药细胞,逆转肿瘤多药耐药性;P-糖蛋白(P-glycoprotein,P-gp)表达水平测定表明,Rev可以显著下调耐药细胞中P-gp的表达,抑制细胞内紫杉醇的外排,同时靶向纳米粒可提高药物的摄取量,从而有效逆转肿瘤细胞的耐药性;在体内抗肿瘤活性研究中,FB-nano/PTX-Rev组的裸鼠体重增加,有效降低游离紫杉醇引发的毒性及副作用,提高药物体内用药安全;体内逆转肿瘤多药耐药效果研究显示,FB-nano/PTX-Rev组表现出最强的耐药肿瘤抑制作用,肿瘤生长抑制率为72.5%。结论FB-nano/PTX-Rev通过肿瘤靶向功能及抑制P-gp的表达,增加药物在耐药肿瘤细胞内的摄取,减少其外排,达到有效的逆转肿瘤多药耐药效果。OBJECTIVE To study the mechanism and activity of reversing multidrug resistance by paclitaxel and resveratrol co-loaded targeting nanoparticles(FB-nano/PTX-Rev).METHODS The ability of reversing multidrug resistance was studied by live/dead cell staining.The mechanism of reversing multidrug resistance was explored by testing P-gpexpression.The in vivo safety and reversing multidrug resistance activity of nanoparticles with paclitaxel and resveratrol co-loadedwere evaluated in MDA-MB-231/taxol tumor bearing mice.RESULTS The live/dead cell staining showed severe dead area in the FB-nano/PTX-Rev group,indicated that FB-nano/PTX-Rev could kill the drug-resistant cells effectively and have the ability of reversing multidrug resistance.The P-glycoprotein(P-gp)detection experiments showed that resveratrol significantly decreased P-gplevel and inhibited the efflux of paclitaxel in drug-resistant cells,meanwhile the targeting nanoparticles increased the drug uptake to achieve efficient reversal of drug resistance.In vivo anti-tumor activity study,the increase of body weight in the mice groups treated with FB-nano/PTX-Rev indicated that the nanoparticles could reduce the side effects and toxicity induced by free PTX and increase the safety in vivo.FB-nano/PTX-Rev exhibited outstanding tumor inhibition effect with tumor growth inhibition rates 72.5%.CONCLUSION FB-nano/PTX-Rev with tumor targeting and inhibiting P-gpexpression function by increasing drug uptake and reducing drug efflux in drug-resistant tumor cells,produced marked activity of reversing multidrug resistance.

关 键 词：紫杉醇 白藜芦醇 靶向 纳米粒 肿瘤多药耐药 

分 类 号：R944[医药卫生—药剂学]