桔梗-莪术药对对口服纳米粒细胞摄取的影响及体外抑制乳腺癌转移作用的研究  

Effects of Platycodonis Radix-Curcumae Rhizoma on oral nanoparticle uptake and in vitro inhibition against breast cancer metastasis

作　　者：施江培 张荣光 顾笑妍 孙颖玮 冯年平[1] 刘颖[1] SHI Jiang-pei;ZHANG Rong-guang;GU Xiao-yan;SUN Ying-wei;FENG Nian-ping;LIU Ying(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中药学院,上海201203

出　　处：《中国中药杂志》2023年第9期2419-2425,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82173988,81773913)。

摘　　要：基于对肿瘤细胞及肿瘤微环境发挥联合作用抑制转移,该文将抑制肿瘤细胞增殖和转移的桔梗-莪术中药药对与调控肿瘤微环境的中药活性成分水飞蓟宾纳米粒联合,研究该药对对纳米粒细胞摄取的影响及体外抑制乳腺癌增殖迁移的作用,为促进纳米粒口服吸收及增强药效提供实验基础。采用纳米沉淀法制备载水飞蓟宾脂质聚合物纳米粒(NPs),透射电镜观测纳米粒形态。该纳米粒呈球形或类球形,具有壳核结构,其平均粒径为107.4 nm,Zeta电位为-27.53 mV。采用体外Caco-2/E12共培养细胞模型和激光共聚焦显微镜观察结果表明药对可增强对纳米粒的细胞摄取。利用激光共聚焦逐层扫描研究小鼠在体纳米粒肠细胞摄取,药对可增强肠绒毛细胞对纳米粒的摄取。分别利用小鼠乳腺癌4T1细胞以及共培养4T1/WML2细胞模型考察纳米粒对乳腺癌4T1细胞增殖和迁移的抑制作用。CCK8法测定细胞增殖实验研究结果表明含药对NPs可增强对4T1乳腺癌细胞增殖抑制作用。细胞划痕实验结果表明含药对NPs可增强对4T1乳腺癌细胞迁移抑制作用。该文丰富了中药纳米载体的口服吸收研究,也为更好地发挥中医药优势抑制乳腺癌转移提供了新思路。This study combined the herbal pair Platycodonis Radix-Curcumae Rhizoma(PR-CR)possessing an inhibitory effect on tumor cell proliferation and metastasis with the active component of traditional Chinese medicine(TCM)silibinin-loaded nanoparticles(NPs)with a regulatory effect on tumor microenvironment based on the joint effect on tumor cells and tumor microenvironment to inhibit cell metastasis.The effects of PR-CR on the cellular uptake of NPs and in vitro inhibition against breast cancer proliferation and metastasis were investigated to provide an experimental basis for improving nanoparticle absorption and enhancing therapeutic effects.Silibinin-loaded lipid-polymer nanoparticles(LPNs)were prepared by the nanoprecipitation method and characterized by transmission electron microscopy.The NPs were spherical or quasi-spherical in shape with obvious core-shell structure.The mean particle size was 107.4 nm,Zeta potential was-27.53 mV.The cellular uptake assay was performed by in vitro Caco-2/E12 coculture cell model and confocal laser scanning microscopy(CLSM),and the results indicated that PR-CR could promote the uptake of NPs.Further,in situ intestinal absorption assay by the CLSM vertical scanning approach showed that PR-CR could promote the absorption of NPs in the enterocytes of mice.The inhibitory effect of NPs on the proliferation and migration of 4T1 cells was analyzed using 4T1 breast cancer cells and co-cultured 4T1/WML2 cells,respectively.The results of the CCK8 assay showed that PR-CR-containing NPs could enhance the inhibition against the proliferation of 4T1 breast cancer cells.The wound healing assay indicated that PR-CR-containing NPs enhanced the inhibition against the migration of 4T1 breast cancer cells.This study enriches the research on oral absorption of TCM NPs and also provides a new idea for utilizing the advantages of TCM to inhibit breast cancer metastasis.

关 键 词：药对 脂质聚合物纳米粒 细胞摄取 细胞迁移 

分 类 号：R285[医药卫生—中药学]