Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells

Background: Deguelin (DGL) is a natural flavonoid reported to exhibit antitumor effects in breast cancer (BC). PEG-PCL (Polyethylene Glycol- Polycaprolactone), as polymeric micelles, has biodegradability and biocompatibility. The aim of this study was to investigate whether the nanoparticular delive...

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Main Authors: Yali Wang, Yang Lan, Liang Wu, Shijin Zhang, Qiang Su, Qin Yang
Format: Article
Language:English
Published: IMR Press 2024-02-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902090
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author Yali Wang
Yang Lan
Liang Wu
Shijin Zhang
Qiang Su
Qin Yang
author_facet Yali Wang
Yang Lan
Liang Wu
Shijin Zhang
Qiang Su
Qin Yang
author_sort Yali Wang
collection DOAJ
description Background: Deguelin (DGL) is a natural flavonoid reported to exhibit antitumor effects in breast cancer (BC). PEG-PCL (Polyethylene Glycol- Polycaprolactone), as polymeric micelles, has biodegradability and biocompatibility. The aim of this study was to investigate whether the nanoparticular delivery system, PEG-PCL could improve the bioavailability of DGL for suppressing proliferation of BC cells. Methods: PEG-PCL polymers were first prepared by ring-opening polymerization, and DGL and paclitaxel (PTX)-loaded PEG-PCL nano-micelles were formulated via the film dispersion method. The composition and molecular weight of PEG-PCL were analyzed by nuclear magnetic resonance and fourier Transform infrared spectroscopy (FTIR) spectra. Particle size, surface potential and hemolytic activity of micelles were assessed by dynamic light scattering, transmission electron microscopy and hemolysis assay, respectively. Then proliferation and apoptosis of MDA-MB-231 and MDA-MB-468 cells were tested with Edu staining, CCK-8, TUNEL staining, and Flow cytometer. Caspase 3 expression was also assessed by Western blot. Results: Our results first indicated that PEG2000-PCL2000 was successfully synthesized. DGL and PTX-loaded PEG-PCL nano-micelles were rounded in shape with a particle size of 35.78 ± 0.35 nm and a surface potential of 2.84 ± 0.27 mV. The micelles had minimal hemolytic activity. Besides, we proved that DGL and PTX-loaded PEG-PCL nano-micelles could suppress proliferation and induce apoptosis in BC cells. The DGL and PTX-loaded PEG-PCL nano-micelles constructed in this study had a prominent inhibitory role on proliferation and a remarkable promotional role on apoptosis in BC cells. Conclusions: This study proposes that nano-micelles formed by PEG-PCL can enhance the cytotoxicity of Paclitaxel against breast cancer cells, and concurrently, the loading of Deguelin may further inhibit cell proliferation. This presents a potential for the development of a novel therapeutic strategy.
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spelling doaj.art-053c70a2964f4662a13adf35092ba1172024-02-29T09:53:15ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-02-012929010.31083/j.fbl2902090S2768-6701(23)01055-9Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer CellsYali Wang0Yang Lan1Liang Wu2Shijin Zhang3Qiang Su4Qin Yang5Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaBackground: Deguelin (DGL) is a natural flavonoid reported to exhibit antitumor effects in breast cancer (BC). PEG-PCL (Polyethylene Glycol- Polycaprolactone), as polymeric micelles, has biodegradability and biocompatibility. The aim of this study was to investigate whether the nanoparticular delivery system, PEG-PCL could improve the bioavailability of DGL for suppressing proliferation of BC cells. Methods: PEG-PCL polymers were first prepared by ring-opening polymerization, and DGL and paclitaxel (PTX)-loaded PEG-PCL nano-micelles were formulated via the film dispersion method. The composition and molecular weight of PEG-PCL were analyzed by nuclear magnetic resonance and fourier Transform infrared spectroscopy (FTIR) spectra. Particle size, surface potential and hemolytic activity of micelles were assessed by dynamic light scattering, transmission electron microscopy and hemolysis assay, respectively. Then proliferation and apoptosis of MDA-MB-231 and MDA-MB-468 cells were tested with Edu staining, CCK-8, TUNEL staining, and Flow cytometer. Caspase 3 expression was also assessed by Western blot. Results: Our results first indicated that PEG2000-PCL2000 was successfully synthesized. DGL and PTX-loaded PEG-PCL nano-micelles were rounded in shape with a particle size of 35.78 ± 0.35 nm and a surface potential of 2.84 ± 0.27 mV. The micelles had minimal hemolytic activity. Besides, we proved that DGL and PTX-loaded PEG-PCL nano-micelles could suppress proliferation and induce apoptosis in BC cells. The DGL and PTX-loaded PEG-PCL nano-micelles constructed in this study had a prominent inhibitory role on proliferation and a remarkable promotional role on apoptosis in BC cells. Conclusions: This study proposes that nano-micelles formed by PEG-PCL can enhance the cytotoxicity of Paclitaxel against breast cancer cells, and concurrently, the loading of Deguelin may further inhibit cell proliferation. This presents a potential for the development of a novel therapeutic strategy.https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902090peg-pcldeguelinpaclitaxelbreast cancerapoptosisproliferation
spellingShingle Yali Wang
Yang Lan
Liang Wu
Shijin Zhang
Qiang Su
Qin Yang
Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
Frontiers in Bioscience-Landmark
peg-pcl
deguelin
paclitaxel
breast cancer
apoptosis
proliferation
title Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
title_full Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
title_fullStr Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
title_full_unstemmed Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
title_short Deguelin and Paclitaxel Loaded PEG-PCL Nano-Micelles for Suppressing the Proliferation and Inducing Apoptosis of Breast Cancer Cells
title_sort deguelin and paclitaxel loaded peg pcl nano micelles for suppressing the proliferation and inducing apoptosis of breast cancer cells
topic peg-pcl
deguelin
paclitaxel
breast cancer
apoptosis
proliferation
url https://www.imrpress.com/journal/FBL/29/2/10.31083/j.fbl2902090
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