Abstract
In the present study, the antitumoral potential of three gel formulations loaded with carbon dots prepared from N-hydroxyphthalimide (CD-NHF) was examined and the influence of the gels on two types of skin melanoma cell lines and two types of breast cancer cell lines in 2D (cultured cells in normal plastic plates) and 3D (Matrigel) models was investigated. Antitumoral gels based on sodium alginate (AS), carboxymethyl cellulose (CMC), and the carbomer Ultrez 10 (CARB) loaded with CD-NHF were developed according to an adapted method reported by Hellerbach. Viscoelastic properties of CD-NHF-loaded gels were analyzed by rheological analysis. Also, for both CD-NHF and CD-NHF-loaded gels, the fluorescence properties were analyzed. Cell proliferation, apoptosis, and mitochondrial activity were analyzed according to basic methods used to evaluate modulatory activities of putative anticancer agents, which include reference cancer cell line culture assays in both classic 2D and 3D cultures. Using the rheological measurements, the mechanical properties of gel formulations were analyzed; all samples presented gel-like rheological characteristics. The presence of CD-NHF within the gels induces a slight decrease of the dynamic moduli, indicating a flexible gel structure. The fluorescence investigations showed that for the gel-loaded CD-NHF, the most intense emission peak was located at 370 nm (upon excitation at 330 nm). 3D cell cultures displayed visibly larger structure of tumor cells with less active phenotype appearance. The in vitro results for tested CD-NHF-loaded gel formulations revealed that the new composites are able to affect the number, size, and cellular organization of spheroids and impact individual tumor cell ability to proliferate and aggregate in spheroids.
Highlights
It has been reported that approximately 8 million people die from different types of cancer each year in the world; including breast, lung, liver, skin, and brain cancers, etc
We focus on the embedding of N-hydroxyphthalimide carbon dots (CD-NHF) in different continuous matrices formed of natural or synthetic (CARB) polymers
Physical gel formulations based on carbomer Ultrez 10 (CARB), AS, and carboxymethyl cellulose (CMC) were synthesized according to a slightly modified version of the method reported by Hellerbach et al [19]
Summary
It has been reported that approximately 8 million people die from different types of cancer each year in the world; including breast, lung, liver, skin, and brain cancers, etc. The main therapeutic methods for cancer treatment remain surgery and chemotherapy; researchers have made enormous efforts in the last years to develop new compounds that are better tolerated by patients during cancer therapy. Enhanced topical delivery of the active principle to the target site, including those for cancer therapy, can be achieved by noninvasive drug delivery systems which can ensure sustained therapy with a single application, avoiding first-pass hepatic metabolism, gastric degradation, or frequent dosing and the inconvenience of parenterals [2]. Different types of natural or synthetic polymers have been used to prepare polymer–drug conjugates, produced mainly by physical entrapment of the biologically active principle into macromolecular hydrogels, micro/nanoparticles, or liposomes in therapeutic approaches for the treatment of various cancers
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