Męczyńska-Wielgosz Sylwia, Sikorska Katarzyna, Czerwińska Malwina, Kapka-Skrzypczak Lucyna, Kruszewski Marcin
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland.
Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland.
Int J Mol Sci. 2025 May 16;26(10):4783. doi: 10.3390/ijms26104783.
Internalization of nanoparticles (NPs), including nanoplastic, is one of the key factors determining their toxicity. In this work, we studied the toxicity and mechanisms of the uptake of model fluorescent polystyrene NPs (PS NPs) of three different sizes (30, 50, and 100 nm) in three human cancer cells lines; two originated from gut tissue (HT-29 and Caco-2) and one originated from liver tissue (Hep G2). Toxicity was measured by Neutral Red Assay (NRU), whereas mechanisms of uptake were studied using flow cytometry and different uptake inhibitors. The toxicity of the studied NPs followed a general rule observed for NPs-the smaller ones were more toxic than the larger ones. This relationship was dose dependent; however, the overall toxicity of the studied NPs was very low, despite the significant uptake of PS NPs. Although clathrin- and caveolin-dependent uptake is generally accepted as a major route of NP uptake, the inhibition of both mechanisms did not affect PS NP uptake in the cell lines studied in this work. Further experiments revealed that the major route of PS NP uptake in these cells is a scavenger receptor-mediated uptake.
包括纳米塑料在内的纳米颗粒（NPs）的内化是决定其毒性的关键因素之一。在这项工作中，我们研究了三种不同大小（30、50和100纳米）的模型荧光聚苯乙烯纳米颗粒（PS NPs）在三种人类癌细胞系中的毒性及摄取机制；其中两种源自肠道组织（HT-29和Caco-2），一种源自肝脏组织（Hep G2）。通过中性红试验（NRU）测定毒性，而使用流式细胞术和不同的摄取抑制剂研究摄取机制。所研究的纳米颗粒的毒性遵循纳米颗粒普遍观察到的规律——较小的纳米颗粒比较大的更具毒性。这种关系是剂量依赖性的；然而，尽管PS NPs有大量摄取，但所研究的纳米颗粒的总体毒性非常低。虽然网格蛋白和小窝蛋白依赖性摄取通常被认为是纳米颗粒摄取的主要途径，但在这项工作所研究的细胞系中，对这两种机制的抑制均不影响PS NPs的摄取。进一步的实验表明，这些细胞中PS NPs摄取的主要途径是清道夫受体介导的摄取。
