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血管生成素2-小干扰RNA质粒壳聚糖磁性纳米粒静脉注射的安全性与毒理学

Safety and toxicology of the intravenous administration of Ang2‑siRNA plasmid chitosan magnetic nanoparticles.

作者信息

Shan Xiuying, Xu Tingting, Liu Zhaoliang, Hu Xuefeng, Zhang Yan-Ding, Wang Biao

机构信息

Department of Plastic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.

College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350108, P.R. China.

出版信息

Mol Med Rep. 2017 Feb;15(2):736-742. doi: 10.3892/mmr.2016.6090. Epub 2016 Dec 29.

DOI:10.3892/mmr.2016.6090
PMID:28035391
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5364838/
Abstract

This aim of the present study was to investigate the safety and toxicology of intravenous administration of angiopoietin‑2 (Ang2)‑small interfering (si)RNA plasmid‑chitosan magnetic nanoparticles (CMNPs). Ang2‑CMNPs were constructed and subsequently administered at different doses to mice and rats via the tail vein. The acute (in mice) and chronic toxicity (in rats) were observed. The results of the acute toxicity assay revealed that the LD50 mice was >707.0 mg·kg‑1·d‑1, and the general condition of mice revealed no obvious abnormalities. With the exception of the high dose group (254.6 mg·kg‑1·d‑1), which exhibited partial lung congestion, the other groups exhibited no obvious abnormalities. Results of the chronic toxicity assay demonstrated that the non‑toxic dose of Ang2‑CMNPs in the rat was >35.35 mg·kg‑1·d‑1 for 14 days. The rat general condition and blood biochemistry indexes revealed no obvious abnormality. The blood routine indexes and lung/body ratio of each treatment group were higher when compared with the control group. The middle‑ and high‑dose groups exhibited chronic pulmonary congestion, whilst the low‑dose and control groups exhibited no abnormality. Similarly, the other organs revealed no obvious abnormality. Ang2‑CMNPs have good safety at a certain dose range and may be considered as the target drug carrier.

摘要

本研究的目的是探讨静脉注射血管生成素-2(Ang2)-小干扰(si)RNA质粒-壳聚糖磁性纳米颗粒(CMNPs)的安全性和毒理学。构建了Ang2-CMNPs,随后经尾静脉以不同剂量给予小鼠和大鼠。观察急性(对小鼠)和慢性毒性(对大鼠)。急性毒性试验结果显示,小鼠的半数致死量>707.0 mg·kg-1·d-1,小鼠的一般状况未显示明显异常。除高剂量组(254.6 mg·kg-1·d-1)出现部分肺充血外,其他组均未显示明显异常。慢性毒性试验结果表明,大鼠中Ang2-CMNPs的无毒剂量在14天内>35.35 mg·kg-1·d-1。大鼠的一般状况和血液生化指标未显示明显异常。各治疗组的血常规指标和肺/体比与对照组相比更高。中、高剂量组出现慢性肺充血,而低剂量组和对照组未出现异常。同样,其他器官未显示明显异常。Ang2-CMNPs在一定剂量范围内具有良好的安全性,可被视为靶向药物载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/00f5a70ea388/MMR-15-02-0736-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/7ea8ca6110fd/MMR-15-02-0736-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/67985ccbc6d7/MMR-15-02-0736-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/80e2e023aea7/MMR-15-02-0736-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/0fce2d3f0033/MMR-15-02-0736-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/74834af770b1/MMR-15-02-0736-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/00f5a70ea388/MMR-15-02-0736-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/7ea8ca6110fd/MMR-15-02-0736-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/67985ccbc6d7/MMR-15-02-0736-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/80e2e023aea7/MMR-15-02-0736-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/0fce2d3f0033/MMR-15-02-0736-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/74834af770b1/MMR-15-02-0736-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfa9/5364838/00f5a70ea388/MMR-15-02-0736-g05.jpg

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