MPEG-PCL Nanomicelles Platform for Synergistic Metformin and Chrysin Delivery to Breast Cancer in Mice
| Autor: | Daiqin Luo, Chaofen Zhao, Heran Wang, Li Ran, Jianying Chang, Mingyuan He, Li Yongxia, Xinjun Wang, Yan Luo, Xiaomei Zhong |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Cell Survival Polyesters Mice Nude Antineoplastic Agents Apoptosis Breast Neoplasms Polyethylene Glycols chemistry.chemical_compound Mice Structure-Activity Relationship Cyclin D1 Annexin In vivo Animals Telomerase reverse transcriptase Chrysin Micelles Cell Proliferation Pharmacology Flavonoids Drug Carriers Dose-Response Relationship Drug Molecular Structure Cell growth Mammary Neoplasms Experimental Metformin chemistry Cancer cell Cancer research Molecular Medicine Nanoparticles Female Drug Screening Assays Antitumor |
| Zdroj: | Anti-cancer agents in medicinal chemistry. 22(2) |
| ISSN: | 1875-5992 |
| Popis: | Background: Metformin (MET) is a well-known anti-diabetic drug that also has anti-cancer effects. However, high therapeutic doses of MET on cancer cells and the low efficacy of combinatory therapeutic approaches limit its clinical application. Recent studies have shown that chrysin (CHR) can improve the pharmaceutical efficacy of MET by suppressing human telomerase reverse transcriptase (hTERT) and cyclin D1 gene expression. Objective: This study aimed to develop different ratios of methoxy poly(ethylene glycol)-b-poly(e-caprolactone) (MPEG-PCL) micelles for breast cancer to co-deliver a synergistic CHR/MET combination. Methods: CHR/MET drug-loaded micelles were prepared by modified thin-film hydration.Fourier infrared spectrum, gel permeation chromatography, transmission electron microscopy, and high-performance liquid chromatography were used to evaluate the physicochemical properties of nanostructures. Cell proliferation and cell apoptosis were assessed by MTT and Annexin V-FITC/PI double staining method. The gene expression of hTERT and cyclin D1 was measured by real-time PCR assay. A subcutaneous mouse T47D xenograft model was established to evaluate the in vivo efficiency. Results: When the ratio of MPEG-PCL was 1:1.7, the highest drug loading rate and encapsulation efficiency of CHR (11.31±0.37) and MET (12.22±0.44) were observed. Uniform MPEG-PCL micelles of 51.70±1.91 nm allowed MET to incorporate with CHR, which were co-delivered to breast cancer cells. We demonstrated that CHR/MET co-delivery micelles showed a good synergistic effect on inhibiting proliferation in T47D cells (combination index=0.87) by suppressing hTERT and cyclin D1 gene expression. Compared to the free CHR/MET group, the apoptosis rate on T47D cells by CHR/MET nano-micelles significantly improved from 71.33% to 79.25%. The tumour volume and tumour weight of the CHR/MET group increased more slowly than that of the single-drug treatment group (P Conclusions: We demonstrated that ratiometric CHR/MET micelles could provide an effective technique for the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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