当前位置: X-MOL 学术ACS Nano › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy
ACS Nano ( IF 17.1 ) Pub Date : 2018-02-06 00:00:00 , DOI: 10.1021/acsnano.8b00516
Xianbing Zhu 1, 2 , Xiaoyuan Ji 3 , Na Kong 3, 4 , Yunhan Chen 3 , Morteza Mahmoudi 3 , Xiaoding Xu 3 , Li Ding 1 , Wei Tao 1, 3 , Ting Cai 1 , Yujing Li 3 , Tian Gan 3 , Austin Barrett 3 , Zameer Bharwani 3 , Hongbo Chen 1 , Omid C. Farokhzad 3
Affiliation  

Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (i.e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS2 NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS2 NSs. Based on these findings, we developed a strategy to achieve effective and synergistic in vivo cancer therapy with MoS2 NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy.

中文翻译:

2D MoS 2纳米片对抗胞吐作用增强的协同癌症治疗的细胞内机制理解。

新兴的二维(2D)纳米材料,例如过渡金属二硫化碳(TMD)纳米片(NSs),已显示出在包括癌症纳米医学在内的许多领域中使用的巨大潜力。纳米材料与生物系统的相互作用对于其安全有效的应用至关重要。然而,细胞水平了解这些新兴的纳米材料的二维(的纳米生物相互作用的Ë,胞内机制)仍然遥遥无期。在这里,我们选择二硫化钼(MoS 2)NSs作为代表性的2D纳米材料,以更好地了解它们在癌细胞中的细胞内作用机制,这在它们的命运和功效中都起着重要作用。硫化钼2发现NSs通过三种途径被内在化:网格蛋白→早期内体→溶酶体,小窝→早期内体→溶酶体,以及巨胞吞作用→晚期内体→溶酶体。我们还观察到溶酶体中自噬介导的积累和胞吐作用诱导的MoS 2 NSs外排。基于这些发现,我们制定了一种策略,可通过抑制胞吐途径诱导的损失,用装载有低剂量药物的MoS 2 NS进行有效且协同的体内癌症治疗。据我们所知,这是关于二维纳米材料在细胞中的纳米生物相互作用及其在抗胞吐增强协同癌症治疗中的应用的第一份系统实验报告。
更新日期:2018-02-06
down
wechat
bug