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
CQUM, Centre of Chemistry, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Institut de science et d'ingénierie supramoléculaire (ISIS), Université de Strasbourg, 8 Alle Gaspard Monge, Strasbourg, France; Dept. of Pharmacy, Faculty of Medicine, Atma Jaya Catholic University of Indonesia, Jl. Pluit Raya 2, 14440 Jakarta, Indonesia.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111721. doi: 10.1016/j.msec.2020.111721. Epub 2020 Nov 14.
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 (NH) 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.
沸石具有吸引人的特性，使其成为药物递送系统（DDS）的合适载体。因此，我们将抗癌药物5-氟尿嘧啶（5-FU）负载到两种不同的沸石结构中，即八面沸石（NaY）和L型沸石（LTL），以获得不同的药物递送系统。所制备的药物递送系统在体外使用乳腺癌、结肠直肠癌和黑色素瘤细胞系进行了测试，并在体内使用鸡胚绒毛尿囊膜模型（CAM）进行了测试。两种检测方法均显示对Hs578T乳腺癌细胞的效果最佳，对于封装在L型沸石中的5-氟尿嘧啶具有更高的增效作用。为了揭示参与沸石纳米颗粒内化的内吞机制，在乳腺癌和人乳腺上皮细胞中通过药理学方法抑制内吞作用。结果表明，小窝蛋白介导的过程是沸石纳米颗粒内化的原因。为了提高药物递送系统的疗效，使用氨基（NH）或羧酸（COOH）基团对盘状L型沸石的外表面进行功能化，并涂覆聚-L-赖氨酸（PLL）。表面带正电的功能化LTL纳米颗粒对人类细胞无毒，重要的是，它们的内化速度更快，并且在体内导致更高的肿瘤消退率。总体而言，我们的结果为基于沸石的药物递送系统与癌细胞之间的相互作用机制提供了进一步的见解，并为旨在提高药物递送系统抗癌活性的未来研究铺平了道路。
