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-Methyltestosterone (MT) release for sys...

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Veröffentlicht in:	Molecules (Basel, Switzerland) Jg. 25; H. 5; S. 1181
Hauptverfasser:	Rezaei, Somayeh, Kashanian, Soheila, Bahrami, Yadollah, Cruz, Luis J., Motiei, Marjan
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland MDPI AG 05.03.2020 MDPI
Schlagworte:	17α-methyltestosterone Acids Androgens Antineoplastic Agents, Hormonal - administration & dosage Antineoplastic Agents, Hormonal - chemistry Apoptosis Biomarkers Breast cancer Cancer therapies cd44 Cell Line, Tumor Chemical bonds chitosan Drug Carriers - chemistry Drug Delivery Systems Drugs Female Fourier transforms Humans hyaluronic acid Hyaluronic Acid - chemistry Hydrogen-Ion Concentration Investigations lipoic acid Magnetic Resonance Spectroscopy Methyltestosterone - administration & dosage Methyltestosterone - chemistry Morphology Nanoparticles Nanoparticles - chemistry NMR Nuclear magnetic resonance Oxidation-Reduction - drug effects reduction-responsive nanoparticles Spectroscopy, Fourier Transform Infrared Spectrum analysis X-Ray Diffraction chitosan lipoic acid reduction-responsive nanoparticles 17α-methyltestosterone CD44 hyaluronic acid
ISSN:	1420-3049, 1420-3049
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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.
AbstractList	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. 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.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. 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.
Author	Cruz, Luis J. Bahrami, Yadollah Motiei, Marjan Rezaei, Somayeh Kashanian, Soheila
AuthorAffiliation	2 Translational Nanobiomaterials and Imaging, department of Radiology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, The Netherlands 3 Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran 6 Molecular Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran 1 Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, Iran; somayehrezaei128@gmail.com 4 Department of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia; bahramiyadollah@yahoo.com 5 Department of Pharmacognosy & Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran 7 Centre of Polymer Systems, Tomas Bata University in Zlín, Třída Tomáše Bati 5678, 76001 Zlín, Czech Republic; marjanmotiei@yahoo.com
AuthorAffiliation_xml	– name: 3 Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran – name: 6 Molecular Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran – name: 1 Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah 6714414971, Iran; somayehrezaei128@gmail.com – name: 2 Translational Nanobiomaterials and Imaging, department of Radiology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, The Netherlands – name: 5 Department of Pharmacognosy & Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah 6714415153, Iran – name: 4 Department of Medical Biotechnology, School of Medicine, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia; bahramiyadollah@yahoo.com – name: 7 Centre of Polymer Systems, Tomas Bata University in Zlín, Třída Tomáše Bati 5678, 76001 Zlín, Czech Republic; marjanmotiei@yahoo.com
Author_xml	– sequence: 1 givenname: Somayeh surname: Rezaei fullname: Rezaei, Somayeh – sequence: 2 givenname: Soheila surname: Kashanian fullname: Kashanian, Soheila – sequence: 3 givenname: Yadollah orcidid: 0000-0002-8063-0357 surname: Bahrami fullname: Bahrami, Yadollah – sequence: 4 givenname: Luis J. surname: Cruz fullname: Cruz, Luis J. – sequence: 5 givenname: Marjan orcidid: 0000-0002-5453-2630 surname: Motiei fullname: Motiei, Marjan
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32151062$$D View this record in MEDLINE/PubMed
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Keywords	chitosan lipoic acid reduction-responsive nanoparticles 17α-methyltestosterone CD44 hyaluronic acid
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Snippet	Novel reduction-responsive hyaluronic acid–chitosan–lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast... Novel reduction-responsive hyaluronic acid-chitosan-lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast... Novel reduction-responsive hyaluronic acid−chitosan−lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast...
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SubjectTerms	17α-methyltestosterone Acids Androgens Antineoplastic Agents, Hormonal - administration & dosage Antineoplastic Agents, Hormonal - chemistry Apoptosis Biomarkers Breast cancer Cancer therapies cd44 Cell Line, Tumor Chemical bonds chitosan Drug Carriers - chemistry Drug Delivery Systems Drugs Female Fourier transforms Humans hyaluronic acid Hyaluronic Acid - chemistry Hydrogen-Ion Concentration Investigations lipoic acid Magnetic Resonance Spectroscopy Methyltestosterone - administration & dosage Methyltestosterone - chemistry Morphology Nanoparticles Nanoparticles - chemistry NMR Nuclear magnetic resonance Oxidation-Reduction - drug effects reduction-responsive nanoparticles Spectroscopy, Fourier Transform Infrared Spectrum analysis X-Ray Diffraction
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Title	Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery
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