中国药房2025，Vol.36Issue(14)：1730-1736,7.DOI:10.6039/j.issn.1001-0408.2025.14.07
叶酸修饰的克班宁纳米粒联合超声辐照对M109细胞的体内外靶向作用及抗肿瘤机制
Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultrasound irradiation on M109 cells in vitro and in vivo
摘要
Abstract
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles(FA-Cre@PEG-PLGA NPs,hereinafter referred to as"NPs")combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration,and explore the anti-tumor mechanism.METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells,and the best ultrasound time was selected.Using human lung cancer A549 cells as a control,the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay.The effects of NPs combined with ultrasound irradiation on the migration,invasion,apoptosis,cell cycle and reactive oxygen species(ROS)levels of M109 cells were detected by cell scratch test,Transwell chamber test and flow cytometry at 1 h after administration;the changes of mitochondrial membrane potential(MMP)were observed by fluorescence inverted microscope.A mouse subcutaneous tumor model of M109 cells was constructed,and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology.RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells,and the optimal ultrasound time was 1 h after administration.The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells,and combined with ultrasound irradiation could partially reverse this antagonism.Compared with A549 cells,the uptake rate of NPs in M109 cells was significantly higher(P＜0.01),and ultrasound irradiation could promote cellular uptake.NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases.Compared with control group,the apoptosis rate of M109 cells and ROS level were increased significantly(P＜0.01),while the MMP decreased significantly(P＜0.01)in the different concentration(100,200,300 μg/mL)groups of M109 cells.Compared with the mice in non-ultrasound group,the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced(P＜0.05 or P＜0.01).CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo,the anti-tumor mechanism includes inhibiting cell migration and invasion,blocking cell cycle,and inducing apoptosis.关键词
叶酸修饰纳米粒/超声辐照/M109细胞/肿瘤靶向性/抗肿瘤机制Key words
folic acid-modified nanoparticles/ultrasonic irradiation/M109 cells/tumor targeting/anti-tumor mechanism分类
医药卫生引用本文复制引用
张海亮,赵笑雨,梅佳华,潘蕊,唐钧泽,喻锟,薛蕊,李晓飞,程欣..叶酸修饰的克班宁纳米粒联合超声辐照对M109细胞的体内外靶向作用及抗肿瘤机制[J].中国药房,2025,36(14):1730-1736,7.基金项目
国家自然科学基金项目(No.82060723) （No.82060723）
云南省科学技术厅-云南中医药大学应用基础研究联合专项(No.202001AZ070001-008) （No.202001AZ070001-008）
云南省傣医药与彝医药重点实验室开放课题(No.202210SS2206) （No.202210SS2206）
云南省教育厅科学研究基金项目(No.2024Y345) （No.2024Y345）
