Evaluation of apoptotic effects of mPEG-b-PLGA coated iron oxide nanoparticles as a eupatorin carrier on DU-145 and LNCaP human prostate cancer cell lines

Marziyeh Shalchi Tousi; Houri Sepehri; Sepideh Khoee; Mahdi Moridi Farimani; Ladan Delphi; Fariba Mansourizadeh

doi:10.1016/j.jpha.2020.04.002

Volume 11 Issue 1

Feb. 2021

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Article Navigation > Journal of Pharmaceutical Analysis > 2021 > 11(1): 108-121

Marziyeh Shalchi Tousi, Houri Sepehri, Sepideh Khoee, Mahdi Moridi Farimani, Ladan Delphi, Fariba Mansourizadeh. Evaluation of apoptotic effects of mPEG-b-PLGA coated iron oxide nanoparticles as a eupatorin carrier on DU-145 and LNCaP human prostate cancer cell lines[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 108-121. doi: 10.1016/j.jpha.2020.04.002

Citation:

Marziyeh Shalchi Tousi, Houri Sepehri, Sepideh Khoee, Mahdi Moridi Farimani, Ladan Delphi, Fariba Mansourizadeh. Evaluation of apoptotic effects of mPEG-b-PLGA coated iron oxide nanoparticles as a eupatorin carrier on DU-145 and LNCaP human prostate cancer cell lines[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 108-121. doi: 10.1016/j.jpha.2020.04.002

Citation:

Marziyeh Shalchi Tousi, Houri Sepehri, Sepideh Khoee, Mahdi Moridi Farimani, Ladan Delphi, Fariba Mansourizadeh. Evaluation of apoptotic effects of mPEG-b-PLGA coated iron oxide nanoparticles as a eupatorin carrier on DU-145 and LNCaP human prostate cancer cell lines[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 108-121. doi: 10.1016/j.jpha.2020.04.002

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Evaluation of apoptotic effects of mPEG-b-PLGA coated iron oxide nanoparticles as a eupatorin carrier on DU-145 and LNCaP human prostate cancer cell lines

doi: 10.1016/j.jpha.2020.04.002

a. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran;
b. Polymer Chemistry Department, School of Science, University of Tehran, Tehran, Iran;
c. Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran

Funds:

We acknowledge the contribution of Reza Karimi and Dr. Akram Mokhtarzadeh Khanghahi for their helpful assistance.

Received Date: Oct. 14, 2019
Accepted Date: Apr. 10, 2020
Rev Recd Date: Apr. 02, 2020
Available Online: Jan. 24, 2022
Publish Date: Feb. 15, 2021

Abstract

Abstract

Many studies have so far confirmed the efficiency of phytochemicals in the treatment of prostate cancer. Eupatorin, a flavonoid with a wide range of phytomedical activities, suppresses proliferation of and induces apoptosis of multiple cancer cell lines. However, low solubility, poor bioavailability, and rapid degradation limit its efficacy. The aim of our study was to evaluate whether the use of mPEG-b-poly (lactic-co-glycolic) acid (PLGA) coated iron oxide nanoparticles as a carrier could enhance the therapeutic efficacy of eupatorin in DU-145 and LNcaP human prostate cancer cell lines. Nanoparticles were prepared by the co-precipitation method and were fully characterized for morphology, surface charge, particle size, drug loading, encapsulation efficiency and in vitro drug-release profile. The inhibitory effect of nanoparticles on cell viability was evaluated by MTT test. Apoptosis was then determined by Hoechest staining, cell cycle analysis, NO production, annexin/propidium iodide (PI) assay, and Western blotting. The results indicated that eupatorin was successfully entrapped in Fe₃O₄@mPEG-b-PLGA nanoparticles with an efficacy of (90.99 ± 2.1)%. The nanoparticle’s size was around (58.5 ± 4) nm with a negative surface charge [(−34.16 ± 1.3) mV]. In vitro release investigation showed a 30% initial burst release of eupatorin in 24 h, followed by sustained release over 200 h. The MTT assay indicated that eupatorin-loaded Fe₃O₄@mPEG-b-PLGA nanoparticles exhibited a significant decrease in the growth rate of DU-145 and LNcaP cells and their IC50 concentrations were 100 μM and 75 μM, respectively. Next, apoptosis was confirmed by nuclear condensation, enhancement of cell population in the sub-G1 phase and increased NO level. Annexin/PI analysis demonstrated that eupatorin-loaded Fe₃O₄@mPEG-b-PLGA nanoparticles could increase apoptosis and decrease necrosis frequency. Finally, Western blotting analysis confirmed these results and showed that Bax/Bcl-2 ratio and the cleaved caspase-3 level were up-regulated by the designing nanoparticles. Encapsulation of eupatorin in Fe₃O₄@mPEG-b-PLGA nanoparticles increased its anticancer effects in prostate cancer cell lines as compared to free eupatorin. Based on these results, this formulation can provide a sustained eupatorin-delivery system for cancer treatment with the drug remaining active at a significantly lower dose, making it a suitable candidate for pharmacological uses.
- Apoptosis,
- Eupatorin,
- Nanoparticles,
- Prostate cancer

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References(67)

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