1. Academic Validation
  2. Polyethylenimine-Modified Mesoporous Silica Nanoparticles Induce a Survival Mechanism in Vascular Endothelial Cells via Microvesicle-Mediated Autophagosome Release

Polyethylenimine-Modified Mesoporous Silica Nanoparticles Induce a Survival Mechanism in Vascular Endothelial Cells via Microvesicle-Mediated Autophagosome Release

  • ACS Nano. 2021 Jun 22;15(6):10640-10658. doi: 10.1021/acsnano.1c03456.
Lu Zhang 1 Gaoqing Feng 1 Shuoye Yang 1 Bin Liu 1 Yakun Niu 1 Pei Fan 1 Zhihui Liu 1 Jingxuan Chen 1 Liuqing Cui 1 Guangzhou Zhou 1 Hongjuan Jing 1 Jing Liu 2 Yunpeng Shen 1
Affiliations

Affiliations

  • 1 College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001, China.
  • 2 Laboratory of Microvascular Medicine, Medical Research Center, the First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China.
Abstract

Surface-modified mesoporous silica nanoparticles (MSNs) have attracted more and more attention as promising Materials for biomolecule delivery. However, the lack of detailed evaluation relevant to the potential cytotoxicity of these MSNs is still a major obstacle for their applications. Unlike the bare MSNs and amino- or liposome-modified MSNs, we found that polyethylenimine-modified MSNs (MSNs-PEI) had no obvious toxicity to human umbilical vein endothelial cells (HUVECs) at the concentrations up to 100 μg/mL. However, MSNs-PEI induced autophagosomes accumulation by blocking their fusion with lysosomes, an essential mechanism for the cytotoxicity of many nanoparticles (NPs). Thus, we predicted that an alternative pathway for autophagosome clearance exists in HUVECs to relieve autophagic stress induced by MSNs-PEI. We found that MSNs-PEI prevented STX17 loading onto autophagosomes instead of influencing lysosomal pH or proteolytic activity. MSNs-PEI induced the structural alternation of the Cytoskeleton but did not cause endoplasmic reticulum stress. The accumulated autophagosomes were released to the extracellular space via microvesicles (MVs) when the autophagic degradation was blocked by MSNs-PEI. More importantly, blockade of either autophagosome formation or release caused the accumulation of damaged mitochondria and excessive ROS production in the MSNs-PEI-treated HUVECs, which in turn led to cell death. Thus, we propose here that the MV-mediated autophagosome release, a compensation mechanism, allows the vascular endothelial cell survival when the degradation of autophagosomes is blocked by MSNs-PEI. Accordingly, promoting the release of accumulated autophagosomes may be a protective strategy against the endothelial toxicity of NPs.

Keywords

autophagosome release; autophagy; cytoskeleton; microvesicle; polyethylenimine-modified mesoporous silica nanoparticles; vascular endothelia cell.

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