NanoDelivery Lab, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, Italy.
School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
Nanoscale. 2024 Sep 12;16(35):16671-16683. doi: 10.1039/d4nr01850h.
Pollution from micro- and nanoplastics (MNPs) has long been a topic of concern due to its potential impact on human health. MNPs can circulate through human blood and, thus far, have been found in the lungs, spleen, stomach, liver, kidneys and even in the brain, placenta, and breast milk. While data are already available on the adverse biological effects of pristine MNPs ( oxidative stress, inflammation, cytotoxicity, and even cancer induction), no report thus far clarified whether the same effects are modulated by the formation of a protein corona around MNPs. To this end, here we use pristine and human-plasma pre-coated polystyrene (PS) nanoparticles (NPs) and investigate them in cultured breast cancer cells both in terms of internalization and cell biochemical response to the exposure. It is found that pristine NPs tend to stick to the cell membrane and inhibit HER-2-driven signaling pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways, which are associated with cancer cell survival and growth. By contrast, the formation of a protein corona around the same NPs can promote their uptake by endocytic vesicles and final sequestration within lysosomes. Of note is that such intracellular fate of PS-NPs is associated with mitigation of the biochemical alterations of the phosphorylated AKT (pAKT)/AKT and phosphorylated ERK (pERK)/ERK levels. These findings provide the distribution of NPs in human breast cancer cells, may broaden our understanding of the interactions between NPs and breast cancer cells and underscore the crucial role of the protein corona in modulating the impact of MNPs on human health.
由于微塑料和纳米塑料 (MNPs) 对人类健康的潜在影响,它们的污染一直是一个备受关注的话题。MNPs 可以在人体血液中循环,迄今为止,已在肺部、脾脏、胃、肝脏、肾脏,甚至大脑、胎盘和母乳中发现。虽然已经有关于原始 MNPs 的不良生物学效应(氧化应激、炎症、细胞毒性,甚至致癌诱导)的数据,但迄今为止没有报告澄清 MNPs 周围形成蛋白质冠是否会调节这些效应。为此,在这里我们使用原始和经人血浆预处理的聚苯乙烯 (PS) 纳米颗粒 (NPs),并在培养的乳腺癌细胞中研究它们,包括内化和细胞生化对暴露的反应。结果发现,原始 NPs 倾向于粘在细胞膜上并抑制 HER-2 驱动的信号通路,包括磷脂酰肌醇-3-激酶 (PI3K)/蛋白激酶 B (AKT) 和丝裂原活化蛋白激酶 (MAPK)/细胞外信号调节激酶 (ERK) 通路,这些通路与癌细胞的存活和生长有关。相比之下,相同 NPs 周围形成蛋白质冠可以促进它们被内吞小泡摄取,并最终被隔离在溶酶体中。值得注意的是,PS-NPs 的这种细胞内命运与磷酸化 AKT (pAKT)/AKT 和磷酸化 ERK (pERK)/ERK 水平的生化改变缓解有关。这些发现提供了 NPs 在人乳腺癌细胞中的分布情况,可能拓宽了我们对 NPs 与乳腺癌细胞相互作用的理解,并强调了蛋白质冠在调节 MNPs 对人类健康影响方面的关键作用。