Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery
Molecules, vol. 25, pp. 1181
Abstract
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.
Authors 4
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Soheila Kashanian corresponding
Razi University · Kermanshah University of Medical Sciences
Affiliation as printed
Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, Iran
Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
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Flinders University · Kermanshah University of Medical Sciences
Affiliation as printed
Department of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia
Department of Pharmacognosy & Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran
Molecular Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran
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Luis Javier Cruz corresponding Aachen Translational Nanobiomaterials and Imaging Department of Radiology, Leiden University Medical Center
Leiden University · Leiden University Medical Center
Affiliation as printed
Translational Nanobiomaterials and Imaging, department of Radiology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, The Netherlands
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Affiliation as printed
Centre of Polymer Systems, Tomas Bata University in Zlín, Třída Tomáše Bati 5678, 76001 Zlín, Czech Republic
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