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.
Highlights
Chemotherapeutic agents inhibit tumor growth, angiogenesis and metastasis, and increase the apoptosis of cancer cells through different mechanisms
Peaks areand with Chitosan-Lipoic acid (CSLA)-NPs, the changes can be ascribed to the formation of the amidic bond between CS
These results showed that hyaluronic acid–chitosan–lipoic acid (HACSLA)-NPs have the ability to target Cluster of Differentiation 44 (CD44)-positive cells and deliver and release MT into them
Summary
Chemotherapeutic agents inhibit tumor growth, angiogenesis and metastasis, and increase the apoptosis of cancer cells through different mechanisms. These agents are used orally, and their administration is limited by poor aqueous solubility and bioavailability. Molecules 2020, 25, 1181 cannot take drugs via the oral route, poor aqueous solubility hinders their intravenous administration. The increase of the drug dose clinically to achieve the therapeutic concentrations at the target tissue can induce toxicity. Testosterone and its esters are considered important agents in the management of advanced mammary cancer. Their application is restricted by the parental administration requirement
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