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Surface functionalization of zeolite-based drug delivery systems enhances their antitumoral activity in vivo
Biomaterials Advances ( IF 5.5 ) Pub Date : 2020-11-14 , DOI: 10.1016/j.msec.2020.111721
Natália Vilaça , Ana Raquel Bertão , Eko Adi Prasetyanto , Sara Granja , Marta Costa , Rui Fernandes , Francisco Figueiredo , António M. Fonseca , Luisa De Cola , Fátima Baltazar , Isabel C. Neves

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.



中文翻译:

基于沸石的药物递送系统的表面功能化可增强其体内抗肿瘤活性

沸石具有吸引人的特性,使其成为药物输送系统(DDS)的合适载体。因此,我们将抗癌药5-氟尿嘧啶(5-FU)装入了两种不同的沸石结构,八面沸石(NaY)和Linde L型(LTL),以获得不同的DDS。使用乳腺癌,结肠直肠癌和黑色素瘤细胞系在体外对制备的DDS进行体内测试使用鸡胚绒膜尿囊膜模型(CAM)。两种测定均显示出对Hs578T乳腺癌细胞的最佳结果,对包裹在沸石LTL中的5-FU的增强作用更高。为了揭示参与沸石纳米颗粒内在化的内吞机制,在乳腺癌和上皮性乳腺人类细胞中药理作用抑制了内吞作用。结果表明,caveolin介导的过程负责内部化的沸石纳米粒子。为了提高DDS的效力,使用氨基(NH 2)或羧酸(COOH)基团,并涂有聚L-赖氨酸(PLL)。正功能化的表面LTL纳米粒子显示出对人类细胞无毒,重要的是,它们的内在化更快,并导致体内更高的肿瘤减少率。总体而言,我们的结果为基于沸石的DDS与癌细胞之间相互作用的机制提供了进一步的见识,并为今后旨在改善DDS抗癌活性的研究铺平了道路。

更新日期:2020-11-15
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