Low doses of zeolitic imidazolate framework-8 nanoparticles alter the actin organization and contractility of vascular smooth muscle cells.
Low doses of zeolitic imidazolate framework-8 nanoparticles alter the actin organization and contractility of vascular smooth muscle cells.
复制标题
DOI：
10.1016/j.jhazmat.2021.125514
复制
发表时间：
2021-07-15
影响因子：
13.6
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Kota D;Kang L;Rickel A;Liu J;Smith S;Hong Z;Wang C
沸石咪唑骨架-8（ZIF-8）纳米颗粒已经成为药物递送和控制释放的有前途的平台。考虑到大多数ZIF-8纳米颗粒药物载体被设计为静脉内给药，因此在许多情况下将直接接触血管平滑肌细胞（VSMC），ZIF-8纳米颗粒与VSMC的潜在相互作用需要研究。在这里，研究了低剂量的ZIF-8纳米颗粒对VSMC形态、肌动蛋白组织和收缩性的影响。两种纳米级成像工具，原子力显微镜和直接随机光学重建显微镜显示，即使在通过常规生物化学细胞测定（MTT和LDH测定）被认为是“安全”的浓度（12.5和25 μg/ml）下，ZIF-8纳米颗粒仍然可以引起细胞顶端和基底表面的细胞形态和肌动蛋白细胞骨架组织的变化。这些细胞骨架结构的变化损害了血管平滑肌细胞对血管紧张素II（一种经典的血管收缩剂）的收缩功能。基于细胞内锌和肌动蛋白聚合测定，我们得出结论，由于ZIF-8纳米颗粒的摄取和解离而增加的细胞内Zn 2+浓度可能导致肌动蛋白细胞骨架解体，因为升高的Zn 2+直接破坏肌动蛋白组装过程，导致肌动蛋白组织改变，例如分支和网络。由于VSMC表型变化和收缩性丧失是动脉粥样硬化和相关心血管疾病发展的基础，因此值得注意的是，静脉内施用的这些低剂量的ZIF-8纳米颗粒在心血管风险方面仍然是安全性问题。展望未来，必须重新考虑单独通过生化细胞测定确定的“安全”纳米颗粒剂量，并考虑这些纳米颗粒对VSMC生物物理特性的影响，包括肌动蛋白细胞骨架和细胞形态的变化。
Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles have emerged as a promising platform for drug delivery and controlled release. Considering most ZIF-8 nanoparticle drug carriers are designed to be administered intravenously, and thus would directly contact vascular smooth muscle cells (VSMCs) in many circumstances, the potential interactions of ZIF-8 nanoparticles with VSMCs require investigation. Here, the effects of low doses of ZIF-8 nanoparticles on VSMC morphology, actin organization, and contractility are investigated. Two nanoscale imaging tools, atomic force microscopy, and direct stochastic optical reconstruction microscopy, show that even at the concentrations (12.5 and 25 μg/ml) that were deemed “safe” by conventional biochemical cell assays (MTT and LDH assays), ZIF-8 nanoparticles can still cause changes in cell morphology and actin cytoskeleton organization at the cell apical and basal surfaces. These cytoskeletal structural changes impair the contractility function of VSMCs in response to Angiotensin II, a classic vasoconstrictor. Based on intracellular zinc and actin polymerization assays, we conclude that the increased intracellular Zn2+ concentration due to the uptake and dissociation of ZIF-8 nanoparticles could cause the actin cytoskeleton dis-organization, as the elevated Zn2+ directly disrupts the actin assembly process, leading to altered actin organization such as branches and networks. Since the VSMC phenotype change and loss of contractility are fundamental to the development of atherosclerosis and related cardiovascular diseases, it is worth noting that these low doses of ZIF-8 nanoparticles administered intravenously could still be a safety concern in terms of cardiovascular risks. Moving forward, it is imperative to re-consider the “safe” nanoparticle dosages determined by biochemical cell assays alone, and take into account the impact of these nanoparticles on the biophysical characteristics of VSMCs, including changes in the actin cytoskeleton and cell morphology.
登录
查看更多内容
影响因子：
48
作者：
Dempsey, Graham T.;Vaughan, Joshua C.;Chen, Kok Hao;Bates, Mark;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
8.3
作者：
Hoop, Marcus;Walde, Claudio F.;Pane, Salvador
通讯作者：
Pane, Salvador
影响因子：
15
作者：
Alsaiari, Shahad K.;Patil, Sachin;Khashab, Niveen M.
通讯作者：
Khashab, Niveen M.
DOI：
10.1073/pnas.0508832103
发表时间：
2006-08-08
影响因子：
11.1
作者：
Hayakawa, Akira;Leonard, Deborah;Corvera, Silvia
通讯作者：
Corvera, Silvia
影响因子：
12.8
作者：
Do, Kee Hun;Kim, Min Sung;Bae, Sun Sik
通讯作者：
Bae, Sun Sik