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Preparation and In Vitro Evaluation of 5-Fluorouracil-Loaded PCL Nanoparticles for Breast Cancer Treatment

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Abstract

Breast cancer is a significant public health issue in both developed and developing countries. Chemotherapy is the primary method of treatment to eliminate drug-resistant cells and prevent progenitor cancer cell growth. Polycaprolactone (PCL) is an excellent candidate for sustained drug delivery due to its amphiphilic nature, semi-crystalline form, biodegradability, biocompatibility, and slow drug release profile. This significant property has motivated their relevance, particularly in the area of anticancer drug delivery applications in the various nanoaggregates. Doxorubicin (DOX) and 5-fluorouracil (5-FU) are common anti-cancer drugs used for breast cancer treatment that they can easily incorporate into PCL. In this study, we synthesized the copolymer of PCL, PCL-DOX-FU, and performed characterization tests (Fourier transform infrared (FTIR), scanning electron microscopy (SEM)).We prepared a breast cancer cell line and evaluated the viability of cultured cells using the MTT test in different treatment groups (PCL, DOX-5FU, DOX, FU) at three different time points (24 h, 48 h, 72 h), and at different concentrations (9, 25, 50, 70 µg/ml). Additionally, we determined the expression rate of Bax and BCL-2 as apoptotic activator genes in treatment groups via real-time PCR techniques. Our data confirms that there are interactions between the active groups in PCL and DOX, as well as 5-FU drugs. After 72 h, a significant decrease was observed at concentrations of 50 and 70. Furthermore, the expression levels of Bcl2 and Bax were significantly reduced in cells treated with DOX, 5-FU, and DOX-5-FU-PCL nanoparticles. Our objective was to produce a nanocarrier system by coating magnetic nanoparticles with FOX-5-FU-PCL and evaluate its impact on the survival of MDA-MB-231 breast cancer cells. Our findings demonstrate that this method was highly successful in enhancing drug delivery efficiency for cancer treatment. However, further investigations are necessary to fully understand the safety and efficacy of these nanoparticles for clinical use.

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Data Availability

Sharing does not apply to this article as no data sets were generated. Data analysis in the current study was performed using publicly available datasets.

Abbreviations

PCL:

Polycaprolactone

5-FU:

5-fluorouracil

DOX:

Doxorubicin

SLNs:

Solid lipid nanoparticles

SiNP:

Silica nanoparticles

FUTP:

Fluorouridine triphosphate

FdUMP:

Fluorodeoxyuridine monophosphate

FdUTP:

Fluorodeoxyuridine triphosphate

TS:

Thymidylate synthase

MTT:

3-(4,5-dimethyl thiazol-2-yl)2,5-diphenyl-tetrazolium bromide)

DMSO:

Dimethyl sulfoxide

FTIR:

Fourier transform infrared

SEM:

Scanning electron microscopy

CDKs:

Cyclin-dependent kinases

Bcl2:

B-cell lymphoma 2

Bax:

Associated X protein

PEG:

Poly(ethylene glycol)

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Acknowledgements

The authors would like to thank the Department of Clinical Science, Science and Research Branch, Islamic Azad University.

Funding

This study was funded by the Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences (Grant No.: 64726).

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Authors and Affiliations

  1. Department of Pharmacology, Science and Research Islamic Azad University, Tehran, Iran

    Seyyed Hossein Fattahi

  2. Department of Veterinary Surgery, Faculty of Veterinary Science, Tehran Science and Research Islamic Azad University, Tehran, Iran

    Alireza Jahandideh

  3. Department of Nanotechnology, Faculty of Advanced Medical Science, Tabriz University, Tabriz, Iran

    Abolfazl Akbarzadeh

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  1. Seyyed Hossein Fattahi
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All authors helped in performing and drafting the manuscript. The authors read and approved the final manuscript. AA conceptualized research; AA and AJ supervised research; HF performed research and analyzed data. All authors contributed to the writing and review of the manuscript.

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Correspondence to Alireza Jahandideh or Abolfazl Akbarzadeh.

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The ethical approval for this paper was obtained from the research ethics committee of Tabriz University of Medical Sciences) IR.TBZMED.VCR.REC.1398.436 (IR.TBZMED.VCR.REC.1398.436).

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Fattahi, S.H., Jahandideh, A. & Akbarzadeh, A. Preparation and In Vitro Evaluation of 5-Fluorouracil-Loaded PCL Nanoparticles for Breast Cancer Treatment. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01318-y

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