Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Somayeh RezaeiMarjan Motiei

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 effic...Continue Reading

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Citations

Oct 22, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina MoraruVasile Ostafe
Dec 2, 2020·Materials Science & Engineering. C, Materials for Biological Applications·Shirin MollazadehMostafa Yazdimamaghani
Feb 10, 2021·Nanomaterials·Magdalena Aflori
Feb 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Balaram Ghosh, Swati Biswas

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Methods Mentioned

BETA
hormone substitution therapy
Hormone Replacement Therapy
infrared spectroscopy
acylation
nuclear magnetic resonance
Dynamic light scattering
X-ray
Assay
amidation
ELISA

Software Mentioned

DFFRAC plus X
SPSS
Excel
- Ray Diffraction

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