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.
Zhongguo Zhong Yao Za Zhi. 2023 May;48(9):2419-2425. doi: 10.19540/j.cnki.cjcmm.20230301.301.
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 inhi-bit 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.
本研究将具有抑制肿瘤细胞增殖和转移作用的中药药对桔梗-莪术(PR-CR)与对肿瘤微环境具有调节作用的中药活性成分水飞蓟宾纳米粒(NPs)相结合,基于对肿瘤细胞和肿瘤微环境的联合作用来抑制细胞转移。研究了PR-CR对NPs细胞摄取的影响以及对乳腺癌增殖和转移的体外抑制作用,为提高纳米粒吸收和增强治疗效果提供实验依据。采用纳米沉淀法制备了载水飞蓟宾脂质-聚合物纳米粒(LPNs),并通过透射电子显微镜进行表征。NPs呈球形或准球形,具有明显的核壳结构。平均粒径为107.4nm,Zeta电位为-27.53mV。通过体外Caco-2/E12共培养细胞模型和共聚焦激光扫描显微镜(CLSM)进行细胞摄取实验,结果表明PR-CR可促进NPs的摄取。此外,通过CLSM垂直扫描方法进行的原位肠道吸收实验表明,PR-CR可促进NPs在小鼠肠细胞中的吸收。分别使用4T1乳腺癌细胞和共培养的4T1/WML2细胞分析了NPs对4T1细胞增殖和迁移的抑制作用。CCK8实验结果表明,含PR-CR的NPs可增强对4T1乳腺癌细胞增殖的抑制作用。伤口愈合实验表明,含PR-CR的NPs增强了对4T1乳腺癌细胞迁移的抑制作用。本研究丰富了中药纳米粒口服吸收的研究,也为利用中药优势抑制乳腺癌转移提供了新思路。