Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
- VernacularTitle: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
- Author:
Hailiang ZHANG
1
,
2
;
Xiaoyu ZHAO
1
;
Jiahua MEI
3
;
Rui PAN
1
,
2
;
Junze TANG
1
;
Kun YU
1
;
Rui XUE
3
;
Xiaofei LI
4
;
Xin CHENG
1
,
2
Author Information
1. College of Traditional Chinese Medicine，Yunnan University of Chinese Medicine，Kunming 650500，China
2. Yunnan Key Laboratory of Dai and Yi Medicines，Kunming 650500，China
3. First Clinical Medical College，Yunnan University of Chinese Medicine，Kunming 650500，China
4. Science and Technology Office，Yunnan University of Chinese Medicine，Kunming 650500，China
- Publication Type:Journal Article
- Keywords:
folic acid-modified nanoparticles;
ultrasonic irradiation;
M109 cells;
tumor targeting;
anti-tumor mechanism
- From:
China Pharmacy
2025;36(14):1730-1736
- CountryChina
- Language:Chinese
-
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 958401536@qq.com 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.
