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基于RNA测序的介孔聚多巴胺纳米颗粒经不同暴露途径作用于小鼠后的毒性分析

RNA-Seq Based Toxicity Analysis of Mesoporous Polydopamine Nanoparticles in Mice Following Different Exposure Routes.

作者信息

Huang Zihua, Xie Luoyijun, Zhang Jifan, Li Qiyan, Liu Yulin, Fu Xuemei, Yuan Miaomiao, Li Qingjiao

机构信息

The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

出版信息

Front Bioeng Biotechnol. 2022 Apr 28;10:893608. doi: 10.3389/fbioe.2022.893608. eCollection 2022.

Abstract

Mesoporous polydopamine nanoparticles (MPDA NPs) are promising nanomaterials that have the prospect of clinical application for multi-strategy antitumor therapy, while the biosecurity of MPDA NPs remains indistinct. Here, transcriptome sequencing (RNA-Seq) was performed to systematically reveal the toxicity of MPDA NPs to five categories of organs after three different exposure routes, including intravenous injection, intramuscular injection, and intragastric administration. Our results uncovered that MPDA NPs could be deposited in various organs in small amounts after intravenous administration, not for the other two exposure routes. The number of differentially expressed genes (DEGs) identified in the heart, liver, spleen, lung, and kidney from the intragastric administration group was from 22 to 519. Similarly, the corresponding number was from 23 to 64 for the intramuscular injection group and was from 11 to 153 for the intravenous injection group. Functional enrichment analyses showed 6, 39, and 4 GO terms enriched for DEGs in intragastric administration, intramuscular injection, and intravenous injection groups, respectively. One enriched pathway was revealed in intragastric administration group, while no enriched pathway was found in other groups. Our results indicated that MPDA NPs produced only slight changes at the transcriptome level in mice, which provided new insights for further clinical application of MPDA NPs.

摘要

介孔聚多巴胺纳米颗粒(MPDA NPs)是很有前景的纳米材料,具有多策略抗肿瘤治疗的临床应用前景,而MPDA NPs的生物安全性仍不明确。在此,进行了转录组测序(RNA-Seq),以系统揭示MPDA NPs经三种不同给药途径(包括静脉注射、肌肉注射和胃内给药)后对五类器官的毒性。我们的结果发现,静脉给药后MPDA NPs可少量沉积于各种器官,而其他两种给药途径则不会。胃内给药组在心脏、肝脏、脾脏、肺和肾脏中鉴定出的差异表达基因(DEG)数量为22至519个。同样,肌肉注射组的相应数量为23至64个,静脉注射组为11至153个。功能富集分析显示,胃内给药组、肌肉注射组和静脉注射组分别有6、39和4个GO术语富集于DEG。胃内给药组揭示了一条富集途径,而其他组未发现富集途径。我们的结果表明,MPDA NPs在小鼠转录组水平上仅产生轻微变化,这为MPDA NPs的进一步临床应用提供了新的见解。

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