Surface functionalization of zeolite-based drug delivery systems enhances their antitumoral activity in vivo

• Published in: Materials Science & Engineering C 2021-01, Vol.120, p.111721, Article 111721
• Main Authors: Vilaça, Natália, Bertão, Ana Raquel, Prasetyanto, Eko Adi, Granja, Sara, Costa, Marta, Fernandes, Rui, Figueiredo, Francisco, Fonseca, António M., De Cola, Luisa, Baltazar, Fátima, Neves, Isabel C.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antitumor activity; Biocompatibility; Breast cancer; Cancer models; Carboxylic acids; Caveolin; Chick Chorioallantoic membrane (CAM) assay; Chick Embryo; Chorioallantoic membrane; Colorectal carcinoma; Drug Carriers; Drug delivery; Drug Delivery Systems; Drug delivery systems (DDS); Embryos; Endocytosis; Fluorouracil - pharmacology; Humans; Internalization; Lysine; Materials science; Melanoma; Nanoparticles; Poly-L-lysine; Surface functionalization; Tumor cell lines; Zeolite nanoparticles; Zeolites; Zeolites - pharmacology
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.111721

Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH2) or carboxylic acid (COOH) groups and coated with poly-l-lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity. [Display omitted] •5-FU DDS-based zeolite nanoparticles exhibit good anticancer efficacy in vitro and in vivo.•Zeolite nanoparticles are mainly internalized by a caveolin-mediated process in cancer cells.•NH2 DDS functionalization increases their antitumoral activity in vivo.