共载β-榄香烯和纳米氧化石墨烯的可注射型脂质体水凝胶治疗4T1乳腺癌的作用  

Effect of Injectable Liposome Hydrogels Co-loadingβ-Elemene and Nano Graphene Oxide for Therapy of 4T1 Breast Cancer

作　　者：王子昂 李一菁 陈家琦 朱艳慧[1] 王白燕[2] 贾永艳[1] 祝侠丽[1] WANG Zi'ang;LI Yijing;CHEN Jiaqi;ZHU Yanhui;WANG Baiyan;JIA Yongyan;ZHU Xiali(Henan University of Chinese Medicine,Pharmacy College,Zhengzhou 450046,China;Henan University of Chinese Medicine,Basic Medicine College,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学药学院,郑州450046 [2]河南中医药大学基础医学院,郑州450046

出　　处：《中国现代应用药学》2024年第19期2608-2616,共9页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(81803740);河南省高等学校重点科研项目(23A360007)。

摘　　要：目的结合808 nm激光照射,探讨共载β-榄香烯(β-elemene,ELE)和甘草次酸修饰纳米氧化石墨烯(glycyrrhetinic acid modified nano graphene oxide,GA/NGO)的可注射型脂质体水凝胶(injectable liposome hydrogels,Lip-gel)用于4T1乳腺癌光热-化协同靶向治疗。方法以4T1乳腺癌细胞为模型,采用MTT、激光共聚焦等技术进行细胞抑制和摄取试验;以4T1雌性BALB/c小鼠为模型,采用红外热成像、活体成像、ELISA等方法评价ELE-GA/NGO-Lip-gel的体内分布和抗肿瘤活性。结果与ELE溶液相比,ELE-GA/NGO-Lip-gel能够显著抑制4T1细胞的增殖(P<0.001),并具有浓度和时间依赖性。经瘤内注射给药后,ELE-GA/NGO-Lip-gel在荷瘤小鼠体内具有良好的光热转换效应,且在肿瘤组织的滞留时间较长。药效学试验中ELE-GA/NGO-Lip-gel组小鼠体质量无明显变化、相对肿瘤体积变化较小,HE和TUNEL病理切片结果显示ELE-GA/NGO-Lip-gel可引起荷瘤小鼠的肿瘤细胞出现大面积凋亡。ELE-GA/NGO-Lip-gel可显著降低荷瘤小鼠血清中TNF-α、IFN-γ、IL-6的含量(P<0.001)。结论ELE-GA/NGO-Lip-gel结合近红外光照射后对4T1乳腺癌的体内外抗肿瘤活性增强。OBJECTIVE Triple-negative breast cancer(TNBC)is the most aggressive type of breast cancers with high mortality,high invasion and metastasis,early and frequent recurrence,poor prognosis,and lack of treatment options.Photothermal therapy(PTT)is a safe and powerful techniques used in the treatment of various cancers due to its non-invasiveness,high specificity,low side effects and strong antitumor efficacy as alternative to conventional cancer therapy.Inspired by the many advantages of liposomal hydrogel as an intelligent drug delivery system for chemo-photothermal therapy,an injectable liposomal hydrogels named as ELE-GA/NGO-Lip-gel loaded withβ-elemene(ELE)and glycyrrhetinic acid modified nano graphene oxide(GA/NGO)has been prepared and characterized in author's previous study.Since 4T1 cells has high tumorigenicity and metastasis,and it is a suitable cell line for the in vivo and in vitro study of TNBC,the injectable liposome hydrogel was investigated for photothermal and synergistic targeted therapy of 4T1 breast cancer in this study.The antitumor activity,pharmacodynamics and tissue distribution of ELEGA/NGO-Lip-gel combined with 808 nm laser irradiation were evaluated with 4T1 breast cancer cell and 4T1 bearing female BALB/c mice as the tumor models in vivo and in vitro.METHODS ELE-GA/NGO-Lip-gel was prepared by reverse phase evaporation method and chemical crosslinking method.The encapsulation rate,drug loading rate and the gelling property were investigated.The near-infrared laser irradiation condition was chosen to be 808 nm(2.5 W·cm−2)for 2 min.4T1 breast cancer cells were taken as the model,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),the scratch assay,and laser confocal technology were used for the antitumor activity,cell migration assay and uptake test in vitro.4T1 bearing female BALB/c mice were taken as the model,infrared thermal imaging,in vivo fluorescence imaging,and the antitumor activity were adopted to evaluate the biodistribution and pharmacodynamics of ELE-GA/NGO-Lip-g

关 键 词：Β-榄香烯 纳米氧化石墨烯 脂质体水凝胶 光热-化治疗 4T1乳腺癌 

分 类 号：R965.2[医药卫生—药理学]