A daunting quest to map the reach and risk of nanoplastics

IF 3.2 3区 医学 Q3 ONCOLOGY
Bryn Nelson PhD, William Faquin MD, PhD
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Because they are so small, nanoplastics also are notoriously difficult to measure.</p><p>To quantify them, some researchers extract and burn them and capture the chemical signatures of the various plastics. Gas chromatography–mass spectrometry can isolate and differentiate among those signatures, but the method is not foolproof. Polyethylene plastics and lipid molecules have comparable architectures that can yield deceptively similar signatures, Dr Campen says. In the brain and other high-lipid tissues, tiny fat globules might not fully digest or wash away with existing methods and could be inadvertently added to the plastics tally.</p><p>Even so, a collaborator at Oklahoma State University reported similar results when he tested human brain samples, and Dr Campen found significantly more accumulation in brain and liver tissues collected in 2024 than in tissues dating back to 2016. “The trend of increasing over time was captivating and something we had a lot of confidence in, even if the total magnitude was adjusted up or down because of the way we digest the samples,” he says.</p><p>Dr Campen’s study also documented an even greater accumulation of nanoplastics in 12 preserved brains from individuals with documented dementia. That makes sense, he says, because the blood-brain barrier impairment and inflammation associated with dementia may aid nanoplastics’ uptake. “We have a lot of confidence that there’s more compared to normal brains, but we can’t really say whether it’s cause or effect,” he says.</p><p>Once he had convinced himself that the numbers were real, Dr Campen admits to feeling deep concern. “Nobody’s shown this before. This is very clear in our data, no matter how we revisit the data,” he says. “What next? Is this going to continue? Does our body eventually put up some kind of a defense to stop these things from getting in?” If the amount remains uncertain, Dr Wolff agrees that the trend is ominous.</p><p>In the human body, few plastic particles are larger than 500 nanometers, and some scientists believe that the gut may provide an initial barrier to larger ones. Intriguingly, Dr Campen and other researchers suspect that some larger bits labeled microplastics, such as those found in the placenta, may instead be nanoplastic accumulations that have lined up or have been packaged together as the body’s machinery attempts to move or clear them.</p><p>“Our first clue comes from the liver, where we see these <i>haystacks</i>, if you will, of particles in the lipid droplets of the liver,” he says. Similar groupings have appeared in the kidneys. “Those are clearance organs, and they have a way of handling lipids and other materials, and maybe they’re not efficient at getting rid of plastics, but they’re trying,” he says.</p><p>Nanoplastics, in other words, might hitch a ride on the lipid delivery system to the lipid-rich brain. “We might be showing plastics as high in fatty regions because we’re just measuring fats and we’re wrong,” he says. “Or they’re probably there because they are lipophilic.” Other evidence supports the latter alternative. In whale blubber, with a fat content of approximately 80%, the Campen laboratory has measured a concentration of nanoplastics roughly 10-fold lower than that in the human brain, with its 40%–60% fat content (depending on the region). “So it’s not just fats; there’s something more to it than just interference,” he says.</p><p>For Alan Workman, MD, an assistant professor of rhinology and skull-based surgery at Harvard Medical School and Massachusetts Eye and Ear in Boston, the complex exposure questions, even if resolved, lead to an even bigger one: So what? Even if microplastics and nanoplastics are definitively linked to cancer-causing pathways such as inflammation, “What can we even do about it at this point?” he asks. “How can we limit our exposure if they are causing problems?”</p><p>As with other chemicals of concern, experts such as Dr Wolff say that the best way to reduce the risk is to “turn off the tap.” Such efforts, however, have drawn fierce opposition by the oil and gas industry, including a proposal in the International Plastics Treaty to cap plastic production, and even limited bills in many US jurisdictions that would ban single-use plastic bags.<span><sup>3</sup></span></p><p>Dr Campen is skeptical that any meaningful production caps will be enacted in the near future. “That’s an absurdity,” he says. 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引用次数: 0

Abstract

After researchers documented plastic debris floating in the Sargasso Sea in the early 1970s, a spate of similar discoveries followed suit in other marine waters and within a growing list of aquatic creatures.1 When more recent studies began turning up evidence of microplastics and even smaller nanoplastics in human tissues and organs—blood, lungs, liver, placenta, and testicles among them—worried scientists started asking how much might be accumulating.

Then in 2024, researchers led by Matthew Campen, PhD, MSPH, director of the New Mexico Center for Metals in Biology and Medicine at the University of New Mexico in Albuquerque, delivered a bombshell.2 For the first time, several independent experts told CytoSource, Dr Campen’s team had provided solid evidence that nanoplastics could cross the blood-brain barrier. Megan Wolff, PhD, MPH, executive director of the Physician and Scientist Network Addressing Plastics and Health in New Paltz, New York, calls it the “last frontier” of the human body.

“We did the math and said, well, we see about 5000 micrograms per gram,” Dr Campen recalls. “The brain is about 1400 grams so that works out to—my gosh, there’s about 7 grams of plastic in the brain!” It is the approximate weight of a plastic spoon, he explains. That analogy generated multiple headlines as well as blowback from critics who argued that the numbers could have been inflated by the inclusion of lipid contaminants.

Dr Campen has urged caution over what he concedes is an initial estimate, even as his research has since estimated that the brain may harbor an average of 100 million or more shard-like nanofragments. “We’re comparing it against fresh plastics, and we know we’ve got old plastics in our body,” he says. Because they are so small, nanoplastics also are notoriously difficult to measure.

To quantify them, some researchers extract and burn them and capture the chemical signatures of the various plastics. Gas chromatography–mass spectrometry can isolate and differentiate among those signatures, but the method is not foolproof. Polyethylene plastics and lipid molecules have comparable architectures that can yield deceptively similar signatures, Dr Campen says. In the brain and other high-lipid tissues, tiny fat globules might not fully digest or wash away with existing methods and could be inadvertently added to the plastics tally.

Even so, a collaborator at Oklahoma State University reported similar results when he tested human brain samples, and Dr Campen found significantly more accumulation in brain and liver tissues collected in 2024 than in tissues dating back to 2016. “The trend of increasing over time was captivating and something we had a lot of confidence in, even if the total magnitude was adjusted up or down because of the way we digest the samples,” he says.

Dr Campen’s study also documented an even greater accumulation of nanoplastics in 12 preserved brains from individuals with documented dementia. That makes sense, he says, because the blood-brain barrier impairment and inflammation associated with dementia may aid nanoplastics’ uptake. “We have a lot of confidence that there’s more compared to normal brains, but we can’t really say whether it’s cause or effect,” he says.

Once he had convinced himself that the numbers were real, Dr Campen admits to feeling deep concern. “Nobody’s shown this before. This is very clear in our data, no matter how we revisit the data,” he says. “What next? Is this going to continue? Does our body eventually put up some kind of a defense to stop these things from getting in?” If the amount remains uncertain, Dr Wolff agrees that the trend is ominous.

In the human body, few plastic particles are larger than 500 nanometers, and some scientists believe that the gut may provide an initial barrier to larger ones. Intriguingly, Dr Campen and other researchers suspect that some larger bits labeled microplastics, such as those found in the placenta, may instead be nanoplastic accumulations that have lined up or have been packaged together as the body’s machinery attempts to move or clear them.

“Our first clue comes from the liver, where we see these haystacks, if you will, of particles in the lipid droplets of the liver,” he says. Similar groupings have appeared in the kidneys. “Those are clearance organs, and they have a way of handling lipids and other materials, and maybe they’re not efficient at getting rid of plastics, but they’re trying,” he says.

Nanoplastics, in other words, might hitch a ride on the lipid delivery system to the lipid-rich brain. “We might be showing plastics as high in fatty regions because we’re just measuring fats and we’re wrong,” he says. “Or they’re probably there because they are lipophilic.” Other evidence supports the latter alternative. In whale blubber, with a fat content of approximately 80%, the Campen laboratory has measured a concentration of nanoplastics roughly 10-fold lower than that in the human brain, with its 40%–60% fat content (depending on the region). “So it’s not just fats; there’s something more to it than just interference,” he says.

For Alan Workman, MD, an assistant professor of rhinology and skull-based surgery at Harvard Medical School and Massachusetts Eye and Ear in Boston, the complex exposure questions, even if resolved, lead to an even bigger one: So what? Even if microplastics and nanoplastics are definitively linked to cancer-causing pathways such as inflammation, “What can we even do about it at this point?” he asks. “How can we limit our exposure if they are causing problems?”

As with other chemicals of concern, experts such as Dr Wolff say that the best way to reduce the risk is to “turn off the tap.” Such efforts, however, have drawn fierce opposition by the oil and gas industry, including a proposal in the International Plastics Treaty to cap plastic production, and even limited bills in many US jurisdictions that would ban single-use plastic bags.3

Dr Campen is skeptical that any meaningful production caps will be enacted in the near future. “That’s an absurdity,” he says. Instead, he suggests that an overhaul of how we manage plastic waste might make a difference. “The whole concept of recycling is a joke,” he says, referring to recent studies suggesting that less than 5% of plastic is actually recycled.4 Instead, he points to countries such as Switzerland that are reducing their overall volume through initiatives such as waste-to-energy incineration.

Evidence-based regulations could be aided by more data about exposure routes and comparisons of nanoplastic levels in different populations, though their sheer ubiquity in everything from irrigation water to fertilizer and soil could make such comparisons difficult. “My fear is that so much of our agricultural system is hamstrung by a process that magnifies the plastics into our food chain,” Dr Campen says.

That ubiquity also complicates the task of calculating relative risk because exposure rates are already 100% for most people. Toxicology studies in animal models may help, says Genoa Warner, PhD, an assistant professor of chemistry and environmental science at the New Jersey Institute of Technology in Newark, especially with nanoplastics that are hard to measure on their own. “We feed our animals plastics, we have a control group, and we look to see what kind of health effects we see,” she says. “It’s just one piece of the puzzle, but we don’t necessarily have to be able to see [the nanoparticles] to figure that out.”

What the field really needs, Dr Campen says, is a reliable metric that can link the relative amount of nanoplastics in particular tissues with a higher risk of consequences such as cancer—another admittedly tall order. Since his recent publication, though, multiple research groups have proposed collaborations, including ones on glioblastoma and breast, colorectal, and appendiceal cancers. By working with cancer experts to apply his laboratory’s measurement capabilities, he says, “I think the next few years will be really telling, and we’ll learn a lot.”

Abstract Image

绘制纳米塑料的影响范围和风险是一项艰巨的任务:在关于微塑料和纳米塑料早期研究的两部分系列文章的第二部分中,研究人员发现了遍布人体的微小颗粒,但警告说,量化和降低风险可能很困难。
20世纪70年代初,研究人员记录了马尾藻海中漂浮的塑料碎片,随后在其他海域和越来越多的水生生物中也相继发现了类似的发现当最近的研究开始发现人体组织和器官(包括血液、肺、肝脏、胎盘和睾丸)中存在微塑料甚至更小的纳米塑料的证据时,忧心忡忡的科学家开始询问可能积累了多少塑料。然后在2024年,由新墨西哥大学阿尔伯克基分校新墨西哥生物和医学金属中心主任、MSPH博士马修·坎彭(Matthew Campen)领导的研究人员发布了一个爆炸性消息几位独立专家告诉CytoSource,坎彭博士的团队首次提供了确凿的证据,证明纳米塑料可以穿过血脑屏障。Megan Wolff博士,公共卫生硕士,纽约新帕尔茨塑料与健康医生和科学家网络的执行董事,称其为人体的“最后前沿”。坎彭博士回忆说:“我们做了计算,发现每克含有5000微克。”“大脑大约有1400克,所以算起来——我的天哪,大脑中大约有7克塑料!”他解释说,这大约是一个塑料勺子的重量。这一类比引发了多个头条新闻,也引发了批评人士的反弹,他们认为这些数字可能因包含脂质污染物而被夸大。坎彭博士敦促人们谨慎对待他承认的初步估计,尽管他的研究估计大脑可能平均含有1亿个或更多的碎片状纳米碎片。“我们将其与新鲜塑料进行比较,我们知道我们体内有旧塑料,”他说。因为它们非常小,纳米塑料也是出了名的难以测量。为了量化它们,一些研究人员提取并燃烧它们,并捕捉各种塑料的化学特征。气相色谱-质谱法可以分离和区分这些特征,但该方法不是万无一失的。Campen博士说,聚乙烯塑料和脂质分子具有类似的结构,可以产生看似相似的特征。在大脑和其他高脂组织中,微小的脂肪球可能无法被现有的方法完全消化或洗掉,可能会无意中被添加到塑料中。即便如此,俄克拉荷马州立大学的一位合作者在测试人类大脑样本时也报告了类似的结果,坎彭博士发现,2024年收集的大脑和肝脏组织中的积累量明显高于2016年的组织。他说:“随着时间的推移,这种增加的趋势很吸引人,我们对这种趋势很有信心,即使由于我们消化样本的方式,总幅度会上下调整。”Campen博士的研究还记录了12个被保存下来的痴呆症患者的大脑中纳米塑料的积累量甚至更多。他说,这是有道理的,因为与痴呆症相关的血脑屏障损伤和炎症可能有助于纳米塑料的吸收。他说:“我们很有信心,与正常大脑相比,有更多的大脑,但我们不能真正说这是原因还是结果。”坎彭博士承认,一旦他确信这些数字是真实的,他就会深感担忧。“以前没有人展示过这个。这在我们的数据中非常清楚,无论我们如何重新审视这些数据,”他说。“下一个什么?这种情况会持续下去吗?我们的身体最终会建立某种防御来阻止这些东西进入吗?”如果数量仍然不确定,Wolff博士同意这种趋势是不祥的。在人体内,很少有超过500纳米的塑料颗粒,一些科学家认为,肠道可能会为更大的塑料颗粒提供最初的屏障。有趣的是,坎彭博士和其他研究人员怀疑,一些较大的标记为微塑料的碎片,比如在胎盘中发现的那些,可能是纳米塑料的堆积,它们排列在一起,或者被包装在一起,因为身体的机器试图移动或清除它们。他说:“我们的第一个线索来自肝脏,如果你愿意的话,我们可以在肝脏的脂滴中看到这些颗粒。”类似的分类也出现在肾脏中。他说:“这些是清除器官,它们有处理脂质和其他物质的方法,也许它们在清除塑料方面效率不高,但它们在努力。”换句话说,纳米塑料可能会搭上脂质输送系统的便车,到达富含脂质的大脑。他说:“我们可能会显示塑料在脂肪区含量很高,因为我们只是测量脂肪,我们错了。”“或者它们的存在可能是因为它们是亲脂的。”其他证据支持后一种说法。 在脂肪含量约为80%的鲸脂中,坎彭实验室测量到的纳米塑料浓度大约比人脑中的低10倍,人脑的脂肪含量为40%-60%(取决于区域)。“所以不只是脂肪;除了干扰之外,还有其他因素。”医学博士艾伦·沃克曼(Alan Workman)是哈佛医学院(Harvard Medical School)和波士顿马萨诸塞州眼耳医学中心(Massachusetts Eye and Ear)的鼻科和颅骨外科助理教授,对于他来说,复杂的暴露问题即使解决了,也会导致一个更大的问题:那又怎样?即使微塑料和纳米塑料确实与炎症等致癌途径有关,“在这一点上,我们能做些什么呢?”他问道。“如果它们造成了问题,我们该如何限制我们的风险敞口?”与其他令人担忧的化学物质一样,沃尔夫博士等专家表示,降低风险的最佳方法是“关掉水龙头”。然而,这些努力遭到了石油和天然气行业的强烈反对,其中包括《国际塑料条约》(International Plastics Treaty)中一项限制塑料生产的提议,甚至美国许多司法管辖区都出台了禁止使用一次性塑料袋的有限法案。坎彭博士怀疑在不久的将来是否会颁布任何有意义的生产上限。“这太荒谬了,”他说。相反,他建议彻底改变我们管理塑料垃圾的方式可能会产生影响。他说:“整个回收的概念就是个笑话。”他指的是最近的研究表明,实际上只有不到5%的塑料被回收利用相反,他指出,瑞士等国正在通过垃圾焚烧发电等举措减少垃圾总量。更多关于纳米塑料暴露途径的数据和不同人群中纳米塑料水平的比较可以帮助制定基于证据的法规,尽管从灌溉用水到肥料和土壤,纳米塑料无处不在,这可能会使这种比较变得困难。坎彭博士说:“我担心的是,我们的农业系统在很大程度上受到了一个过程的影响,这个过程将塑料放大到我们的食物链中。”这种无处不在也使计算相对风险的任务变得复杂,因为对大多数人来说,接触率已经是100%。动物模型的毒理学研究可能会有所帮助,热那亚·华纳博士说,他是纽瓦克新泽西理工学院化学和环境科学的助理教授,特别是纳米塑料本身很难测量。她说:“我们用塑料喂养动物,我们有一个对照组,我们看看我们看到了什么样的健康影响。”“这只是谜题的一部分,但我们不一定要能够看到(纳米颗粒)才能弄清楚。”Campen博士说,这个领域真正需要的是一种可靠的指标,可以将特定组织中纳米塑料的相对数量与癌症等后果的高风险联系起来——这是一个公认的艰巨任务。然而,自从他最近发表论文以来,多个研究小组提出了合作,包括胶质母细胞瘤、乳腺癌、结肠直肠癌和阑尾癌。他说,通过与癌症专家合作,应用他的实验室的测量能力,“我认为未来几年将是真正有意义的,我们将学到很多东西。”
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Cytopathology
Cancer Cytopathology 医学-病理学
CiteScore
7.00
自引率
17.60%
发文量
130
审稿时长
1 months
期刊介绍: Cancer Cytopathology provides a unique forum for interaction and dissemination of original research and educational information relevant to the practice of cytopathology and its related oncologic disciplines. The journal strives to have a positive effect on cancer prevention, early detection, diagnosis, and cure by the publication of high-quality content. The mission of Cancer Cytopathology is to present and inform readers of new applications, technological advances, cutting-edge research, novel applications of molecular techniques, and relevant review articles related to cytopathology.
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