Journal of hazardous materials | VOL. 414
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Low doses of zeolitic imidazolate framework-8 nanoparticles alter the actin organization and contractility of vascular smooth muscle cells.

Publication Date Jul 15, 2021

Abstract

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 25µg/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...

Concepts

Zeolitic Imidazolate Framework-8 Nanoparticles Changes In Cell Morphology Vascular Smooth Muscle Cells Vascular Smooth Muscle Cells Morphology Basal Direct Stochastic Optical Reconstruction Microscopy Actin Vascular Smooth Muscle Cells In Response Nanoparticles Doses Of Nanoparticles

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