Preparation of curcumin TPP-PEG-PE nanomicelles with mitochondrial targeting and lysosomal escape functions and its effect on promoting breast cancer cell apoptosis.
10.19540/j.cnki.cjcmm.20200819.303
- Author:
Yin-Hua YUAN
1
;
Qi GUANG
1
;
Shan-Shan ZHANG
1
;
Mi TANG
2
Author Information
1. Cancer Research Center, Zhumadian Central Hospital of Henan Province Zhumadian 463000, China.
2. West China School of Public Health, Sichuan University Chengdu 610039, China.
- Publication Type:Journal Article
- Keywords:
breast cancer cells;
lysosomal escape;
mitochondrial targeting;
orthogonal test;
tumor cell apoptosis
- MeSH:
Apoptosis;
Breast Neoplasms/drug therapy*;
Cell Line, Tumor;
Curcumin/pharmacology*;
Humans;
Lysosomes;
Micelles;
Mitochondria;
Phosphatidylethanolamines;
Polyethylene Glycols
- From:
China Journal of Chinese Materia Medica
2020;45(22):5495-5503
- CountryChina
- Language:Chinese
-
Abstract:
Orthogonal experiments were used to optimize the process parameters of curcumin TPP-PEG-PCL nanomicelles; the particle size, electric potential and morphology under the electron microscope were systematically detected for the curcumin TPP-PEG-PCL nanomicelles; and the stability and in vitro release of the curcumin TPP-PEG-PCL nanomicelles were investigated. With DID fluorescent dye as the fluorescent probe, flow cytometry was used to study the uptake of nanomicelles by breast cancer cells, and laser confocal microscopy was used to study the mitochondrial targeting and lysosomal escape functions of nanomicelles. Under the same dosage conditions, the effect of curcumin TPP-PEG-PCL nanomicelles on promoting the apoptosis of breast cancer cells was evaluated. The optimal particle size of curcumin TPP-PEG-PCL nanomicelle was(17.3±0.3) nm, and the Zeta potential was(14.6±2.6) mV in orthogonal test. Under such conditions, the micelle appeared as regular spheres under the transmission electron microscope. Fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote drug uptake by tumor cells, escape from lysosomal phagocytosis, and target the mitochondria. The cell survival rate and Hoechst staining positive test results showed that curcumin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of breast cancer cells. The curcumin TPP-PEG-PCL micelles can significantly reduce the mitochondrial membrane potential of breast cancer cells, increase the release of cytochrome C, significantly increase the expression of pro-apoptotic protein Bcl-2 and reduce the expression of anti-apoptotic Bax protein. These test results were significantly better than those of curcumin PEG-PCL nanomicelles and curcumin, with statistically significant differences. The results revealed that curcumin TPP-PEG-PCL nanomicelles can well target breast cancer cell mitochondria and escape from the lysosomal capture, thereby enhancing the drug's role in promoting tumor cell apoptosis.
