纳米颗粒治疗疾病的实验研究和临床试验不断增加。然而,由于巨大的成本,进入市场的范围与这些努力无关,几年的发展,以及心脏毒性等脱靶效应。多细胞生物,如秀丽隐杆线虫(C.线虫)可以弥合体外和脊椎动物测试之间的差距,因为它们可以通过3REU关于动物使用的指令,通过简便的实验提供有关全身毒性和特定有害影响的广泛信息。因为线虫咽部与人类心脏有相似之处,我们使用秀丽隐杆线虫评估了药物和聚吡咯纳米颗粒(PpyNPs)的一般和咽部效应。FDA批准的药物的评估,例如普萘洛尔和消旋肾上腺素再现了人类报道的心律失常行为,并支持使用这种小动物模型.因此,由于对心律失常治疗的研究兴趣,对PpyNP进行了评估。通过评估存活率来确认NPs的生物相容性,成长和发展,繁殖,和秀丽隐杆线虫的跨代毒性。有趣的是,NPs增加了两个慢泵突变株中秀丽隐杆线虫的咽泵率,JD21和DA464。此外,NPs随着时间的推移增加了泵送率,持续到排泄后一天。通过测量咽部的钙水平,我们发现PPyNPs对泵送速率的影响可以通过钙信号介导。因此,评估秀丽隐杆线虫的心律失常效应提供了一个简单的系统来测试药物和纳米颗粒,通过PpyNPs阐明。
Experimental studies and clinical trials of
nanoparticles for treating diseases are increasing continuously. However, the reach to the market does not correlate with these efforts due to the enormous cost, several years of development, and off-target effects like cardiotoxicity. Multicellular organisms such as the Caenorhabditis elegans (C. elegans) can bridge the gap between in vitro and vertebrate testing as they can provide extensive information on systemic toxicity and specific harmful effects through facile experimentation following 3R EU directives on animal use. Since the nematodes\' pharynx shares similarities with the human heart, we assessed the general and pharyngeal effects of drugs and polypyrrole
nanoparticles (Ppy NPs) using C. elegans. The evaluation of FDA-approved drugs, such as Propranolol and Racepinephrine reproduced the arrhythmic behavior reported in humans and supported the use of this small animal model. Consequently, Ppy NPs were evaluated due to their research interest in cardiac arrhythmia treatments. The NPs\' biocompatibility was confirmed by assessing survival, growth and development, reproduction, and transgenerational toxicity in C. elegans. Interestingly, the NPs increased the pharyngeal pumping rate of C. elegans in two slow-pumping mutant strains, JD21 and DA464. Moreover, the NPs increased the pumping rate over time, which sustained up to a day post-excretion. By measuring pharyngeal calcium levels, we found that the impact of Ppy NPs on the pumping rate could be mediated through calcium signaling. Thus, evaluating arrhythmic effects in C. elegans offers a simple system to test drugs and
nanoparticles, as elucidated through Ppy NPs.