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Open AccessArticle

Actively Targeted and Redox Responsive Delivery of Anticancer Drug by Chitosan Nanoparticles

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Savinio, Ed. Polifunzionale, 87036 Arcavacata di Rende, Italy
Institute for the Research and the Biomedical Innovation (IRIB)-CNR-Mangone (CS), 00185 Rome, Italy
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 26;
Received: 29 November 2019 / Revised: 20 December 2019 / Accepted: 21 December 2019 / Published: 26 December 2019
(This article belongs to the Special Issue Nanocarriers for Drug Delivery Systems)
The clinical efficacy of methotrexate (MTX) is limited by its poor water solubility, its low bioavailability, and the development of resistance in cancer cells. Herein, we developed novel folate redox-responsive chitosan (FTC) nanoparticles for intracellular MTX delivery. l-Cysteine and folic acid molecules were selected to be covalently linked to chitosan in order to confer it redox responsiveness and active targeting of folate receptors (FRs). NPs based on these novel polymers could possess tumor specificity and a controlled drug release due to the overexpression of FRs and high concentration of reductive agents in the microenvironment of cancer cells. Nanoparticles (NPs) were prepared using an ionotropic gelation technique and characterized in terms of size, morphology, and loading capacity. In vitro drug release profiles exhibited a glutathione (GSH) dependence. In the normal physiological environment, NPs maintained good stability, whereas, in a reducing environment similar to tumor cells, the encapsulated MTX was promptly released. The anticancer activity of MTX-loaded FTC-NPs was also studied by incubating HeLa cells with formulations for various time and concentration intervals. A significant reduction in viability was observed in a dose- and time-dependent manner. In particular, FTC-NPs showed a better inhibition effect on HeLa cancer cell proliferation compared to non-target chitosan-based NPs used as control. The selective cellular uptake of FTC-NPs via FRs was evaluated and confirmed by fluorescence microscopy. Overall, the designed NPs provide an attractive strategy and potential platform for efficient intracellular anticancer drug delivery. View Full-Text
Keywords: redox-responsive; folate-targeting; chitosan nanoparticles; methotrexate; intracellular drug release redox-responsive; folate-targeting; chitosan nanoparticles; methotrexate; intracellular drug release
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MDPI and ACS Style

Mazzotta, E.; De Benedittis, S.; Qualtieri, A.; Muzzalupo, R. Actively Targeted and Redox Responsive Delivery of Anticancer Drug by Chitosan Nanoparticles. Pharmaceutics 2020, 12, 26.

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