基于石墨烯的肿瘤细胞核靶向荧光纳米探针在生殖和后代健康的生殖毒性评价。
Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.
发表日期:2023 Mar 29
作者:
Yuxi Zhang, Qianghua Xue, Xuelian Yin, Lin Zhan, Junfeng Zhang, Murad Khan, Yinghua Wu, Jiale Ju, Yajie Li, Yajun Xu, Wen He, Yanli Wang, Chenchen Li
来源:
MOLECULAR PHARMACEUTICS
摘要:
我们实验室合成了一种新的基于石墨烯的荧光纳米探针用于肿瘤细胞核(GTTNs),它可以穿透细胞膜,特别针对癌细胞核,并且具有极大的临床应用潜力。虽然我们已经进行了关于GTTNs的急性和亚急性毒性研究,但主要结果表明GTTNs几乎没有急性和亚急性毒性。但是,孕育和后代发育毒性的影响作为安全评估的重要部分仍然缺失。在本研究中,我们将GTTNs注入雄性小鼠体内,并测量小鼠的存活状况、睾丸和附睾的组织病理学、睾丸组织的增殖与凋亡、以及小鼠的精子活动力。为了评估雄性小鼠的短期和长期生育能力,不同的雄性小鼠在最后一次治疗后1天和30天内与未处理的雌性小鼠同居,并通过测量幼鼠的数量、体重和器官指数来评估幼鼠的健康参数。结果表明,暴露于GTTNs的雄性小鼠保持了良好的生育能力、睾丸和附睾的健康结构和健康精子的产生。同时,后代与对照组之间没有显著差异。考虑到GTTNs在生物医学应用中具有广阔的前景,我们的研究结果为进一步了解其生物安全性提供了基础。
A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.