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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Vol. 25; no. 5; p. 1181
Main Authors: Rezaei, Somayeh, Kashanian, Soheila, Bahrami, Yadollah, Cruz, Luis J., Motiei, Marjan
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 05.03.2020
MDPI
Subjects:
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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Summary: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
1420-3049
DOI:10.3390/molecules25051181