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Article

Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery

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Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, Iran
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Translational Nanobiomaterials and Imaging, department of Radiology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, The Netherlands
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Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
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Department of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia
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Department of Pharmacognosy & Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran
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Molecular Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran
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Centre of Polymer Systems, Tomas Bata University in Zlín, Třída Tomáše Bati 5678, 76001 Zlín, Czech Republic
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Authors to whom correspondence should be addressed.
Molecules 2020, 25(5), 1181; https://doi.org/10.3390/molecules25051181
Received: 6 February 2020 / Revised: 24 February 2020 / Accepted: 25 February 2020 / Published: 5 March 2020
Novel reduction-responsive hyaluronic acid–chitosan–lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast cancer by targeting Cluster of Differentiation 44 (CD44)-overexpressing cells and reduction-triggered 17α-Methyltestosterone (MT) release for systemic delivery. The effectiveness of these nanoparticles was investigated by different assays, including release rate, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), lactate dehydrogenase (LDH), caspase-3 activity, Rhodamine 123 (RH-123), and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro experiments revealed that Methyltestosterone/Hyaluronic acid–chitosan–lipoic acid nanoparticles (MT/HACSLA-NPs) illustrated a sustained drug release in the absence of glutathione (GSH), while the presence of GSH led to fast MT release. HACSLA-NPs also showed high cellular internalization via CD44 receptors, quick drug release inside the cells, and amended cytotoxicity against positive CD44 BT-20 breast cancer cell line as opposed to negative CD44, Michigan Cancer Foundation-7 (MCF-7) cell line. These findings supported that these novel reduction-responsive NPs can be promising candidates for efficient targeted delivery of therapeutics in cancer therapy. View Full-Text
Keywords: reduction-responsive nanoparticles; hyaluronic acid; chitosan; lipoic acid; CD44; 17α-methyltestosterone reduction-responsive nanoparticles; hyaluronic acid; chitosan; lipoic acid; CD44; 17α-methyltestosterone
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MDPI and ACS Style

Rezaei, S.; Kashanian, S.; Bahrami, Y.; Cruz, L.J.; Motiei, M. Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery. Molecules 2020, 25, 1181. https://doi.org/10.3390/molecules25051181

AMA Style

Rezaei S, Kashanian S, Bahrami Y, Cruz LJ, Motiei M. Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery. Molecules. 2020; 25(5):1181. https://doi.org/10.3390/molecules25051181

Chicago/Turabian Style

Rezaei, Somayeh, Soheila Kashanian, Yadollah Bahrami, Luis J. Cruz, and Marjan Motiei. 2020. "Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery" Molecules 25, no. 5: 1181. https://doi.org/10.3390/molecules25051181

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