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Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence

文献类型：期刊论文

作者Cheng, Yaxin2; Tao, Jinsong2; Zhang, Yaqi3,6,7; Xi, Long2; Han, Run2; Xu, Meng2; Lee, Simon Ming-Yuen2; Ge, Wei5; Gan, Yong1,3,4,6,7; Zheng, Ying2,5
刊名MOLECULAR PHARMACEUTICS
出版日期2023-05-11
卷号20期号:6页码:3187-3201
关键词mesoporous silica nanoparticles (MSNs) toxicity shape shear stress in vitro blood flow model
ISSN号1543-8384
DOI10.1021/acs.molpharmaceut.3c00180
通讯作者Gan, Yong(ygan@simm.ac.cn) ; Zheng, Ying(yzheng@um.edu.mo)
英文摘要Mesoporous silica nanoparticles (MSNs) are widely usedin the biomedicalfield because of their unique and excellent properties. However, thepotential toxicity of different shaped MSNs via injection has notbeen fully studied. This study aims to systematically explore theimpact of shape and shear stress on the toxicity of MSNs after injection.An in vitro blood flow model was developed to investigate the cytotoxicityand the underlying mechanisms of spherical MSNs (S-MSN) and rodlikeMSNs (R-MSN) in human umbilical vein endothelial cells (HUVECs). Theresults suggested that the interactions between MSNs and HUVECs underthe physiological flow conditions were significantly different fromthat under static conditions. Whether under static or flow conditions,R-MSN showed better cellular uptake and less oxidative damage thanS-MSN. The main mechanism of cytotoxicity induced by R-MSN was dueto shear stress-dependent mechanical damage of the cell membrane,while the toxicity of S-MSN was attributed to mechanical damage andoxidative damage. The addition of fetal bovine serum (FBS) alleviatedthe toxicity of S-MSN by reducing cellular uptake and oxidative stressunder static and flow conditions. Moreover, the in vivo results showedthat both S-MSN and R-MSN caused cardiovascular toxicity in zebrafishand mouse models due to the high shear stress, especially in the heart.S-MSN led to severe oxidative damage at the accumulation site, suchas liver, spleen, and lung in mice, while R-MSN did not cause significantoxidative stress. The results of in vitro blood flow and in vivo modelsindicated that particle shape and shear stress are crucial to thebiosafety of MSNs, providing new evidence for the toxicity mechanismsof the injected MSNs.
WOS关键词ENDOTHELIAL-CELLS ; DELIVERY ; BIOCOMPATIBILITY ; PERMEABILITY ; EXCRETION ; TRANSPORT ; CANCER ; SAFETY ; ROS
资助项目Research Grant from Macau Science and Technology Development Fund[0086/2021/A2] ; 2022 Internal Research Grant (IRG) in State Key Laboratory of Quality Research in Chinese Medicine, University of Macau
WOS研究方向Research & Experimental Medicine ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001006647000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/306248]  
专题新药研究国家重点实验室
通讯作者Gan, Yong; Zheng, Ying
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Beijing 100050, Peoples R China
5.Univ Macau, Fac Hlth Sci, Macau 999078, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Cheng, Yaxin,Tao, Jinsong,Zhang, Yaqi,et al. Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence[J]. MOLECULAR PHARMACEUTICS,2023,20(6):3187-3201.
APA Cheng, Yaxin.,Tao, Jinsong.,Zhang, Yaqi.,Xi, Long.,Han, Run.,...&Zheng, Ying.(2023).Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence.MOLECULAR PHARMACEUTICS,20(6),3187-3201.
MLA Cheng, Yaxin,et al."Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence".MOLECULAR PHARMACEUTICS 20.6(2023):3187-3201.

入库方式： OAI收割

来源：上海药物研究所

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