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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Main Authors: Somayeh Rezaei, Soheila Kashanian, Yadollah Bahrami, Luis J. Cruz, Marjan Motiei
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/5/1181
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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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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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AT yadollahbahrami redoxsensitiveandhyaluronicacidfunctionalizednanoparticlesforimprovingbreastcancertreatmentbycytoplasmic17amethyltestosteronedelivery
AT luisjcruz redoxsensitiveandhyaluronicacidfunctionalizednanoparticlesforimprovingbreastcancertreatmentbycytoplasmic17amethyltestosteronedelivery
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