Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery
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-Methyltest...
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MDPI AG
2020-03-01
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author | Somayeh Rezaei Soheila Kashanian Yadollah Bahrami Luis J. Cruz Marjan Motiei |
author_facet | Somayeh Rezaei Soheila Kashanian Yadollah Bahrami Luis J. Cruz Marjan Motiei |
author_sort | Somayeh Rezaei |
collection | DOAJ |
description | 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. |
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issn | 1420-3049 |
language | English |
last_indexed | 2024-04-13T17:27:41Z |
publishDate | 2020-03-01 |
publisher | MDPI AG |
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series | Molecules |
spelling | doaj.art-412f4829fa26444abbf7adcd85c98dc32022-12-22T02:37:42ZengMDPI AGMolecules1420-30492020-03-01255118110.3390/molecules25051181molecules25051181Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone DeliverySomayeh Rezaei0Soheila Kashanian1Yadollah Bahrami2Luis J. Cruz3Marjan Motiei4Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, IranDepartment of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, IranDepartment of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, AustraliaTranslational Nanobiomaterials and Imaging, department of Radiology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, The NetherlandsCentre of Polymer Systems, Tomas Bata University in Zlín, Třída Tomáše Bati 5678, 76001 Zlín, Czech RepublicNovel 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.https://www.mdpi.com/1420-3049/25/5/1181reduction-responsive nanoparticleshyaluronic acidchitosanlipoic acidcd4417α-methyltestosterone |
spellingShingle | Somayeh Rezaei Soheila Kashanian Yadollah Bahrami Luis J. Cruz Marjan Motiei Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery Molecules reduction-responsive nanoparticles hyaluronic acid chitosan lipoic acid cd44 17α-methyltestosterone |
title | Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery |
title_full | Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery |
title_fullStr | Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery |
title_full_unstemmed | Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery |
title_short | Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery |
title_sort | redox sensitive and hyaluronic acid functionalized nanoparticles for improving breast cancer treatment by cytoplasmic 17α methyltestosterone delivery |
topic | reduction-responsive nanoparticles hyaluronic acid chitosan lipoic acid cd44 17α-methyltestosterone |
url | https://www.mdpi.com/1420-3049/25/5/1181 |
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