Mitochondrial targeting function of norcantharidin TPP-PEG-PCL nanomicelles promotes apoptosis of liver tumor cells
10.7501/j.issn.0253-2670.2020.19.013
- VernacularTitle: 具有线粒体靶向功能的载去甲斑蝥素TPP-PEG-PCL纳米胶束促肝肿瘤细胞凋亡研究
- Author:
Li-Li HAN
1
Author Information
1. Cancer Research Center, Cancer Hospital of Zhengzhou University
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Cell uptake;
Lysosomal escape;
Mitochondrial membrane potential;
Mitochondrial targeting;
Nanomicelles;
Norcantharidin;
TPP-PEG-PCL
- From:
Chinese Traditional and Herbal Drugs
2020;51(19):4943-4953
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To prepare norcantharidin TPP-PEG-PCL nanomicelles and study its release in vitro, intracellular transport and promoting effect on hepatoma cell apoptosis. Methods: Thin film hydration method was used to prepare norcantharidin TPP-PEG-PCL nanomicelles, and the particle size, electric potential and microscopic electron microscopy morphological analysis were measured. At the same time, the nanomicelles were evaluated for stability, in vitro release, pharmacokinetics and critical micelle concentration. Coumarin-6 was used as a fluorescent probe to evaluate the uptake of TPP-PEG-PCL nanomicelles in liver tumor cells, lysosomal escape and mitochondrial targeting function; Under the same dosage conditions, the effect of norcantharidin TPP-PEG-PCL nanomicelles on promoting apoptosis of liver tumor cells was evaluated. Results: The cantharidin TPP-PEG-PCL nanomicelles had a particle size of (16.8 ± 0.2) nm, a Zeta potential of (14.3 ± 0.2) mV, and transmission electron microscopy images showed that nanomicelles had a regular spherical shape. The fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote the cellular uptake of drugs, escape lysosomal capture, and finally target aggregation at the mitochondrial site; Cell survival rate and Hoechst staining results showed that cantharidin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of liver tumor cells. Norcantharidin TPP-PEG-PCL nanomicelles can significantly reduce mitochondrial membrane potential, increase intracellular ROS levels, increase pro-apoptotic protein Bcl-2, and reduce resistance. The expression of apoptotic proteins Bax and these pro-apoptotic related experimental results are significantly better than those of norcantharidin PEG-PCL nanomicelles and norcantharidin, which have statistical significance. Conclusion: Norcantharidin TPP-PEG-PCL nanomicelles have good liver tumor cell mitochondrial targeting and promote tumor cell apoptosis, and it is a potentially effective drug delivery system for targeting tumor cell mitochondria.
