Chen Yingxian, Rosano Vinicio, Lozano Neus, Shin YuYoung, Mironov Aleksandr, Spiller David, Casiraghi Cinzia, Kostarelos Kostas, Vranic Sandra
Nano-Cell Biology Lab, Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Centre for Nanotechnology in Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
J Nanobiotechnology. 2025 May 30;23(1):393. doi: 10.1186/s12951-025-03400-3.
Understanding how graphene oxide (GO) interacts with cells is crucial for its safe and efficient biomedical applications. Despite extensive research, a systematic investigation using a panel of cell lines, thoroughly characterized label-free nanomaterials, and complementary analytical techniques is lacking. Here, we examined the uptake of thin GO sheets with distinct lateral dimensions in 13 cell lines: 8 cancer (HeLa, A549, PC3, DU-145, LNCaP, SW-480, SH-SY5Y, U87-MG) and 5 non-cancer (BEAS-2B, NIH/3T3, PNT-2, HaCaT, 293T), using confocal microscopy, transmission electron microscopy, and flow cytometry. Our results reveal a striking difference in GO uptake: non-cancer cells internalized GO efficiently, while in cancer cells, GO predominantly interacted with the plasma membrane, showing minimal to no internalization. Comparison to other nanomaterials (polystyrene beads and graphene flakes) confirmed that cancer cells internalize materials similarly to non-cancer cells, indicating GO-specific interactions. We identified that GO's thinness plays important role in this differential uptake. More importantly, GO disrupts the actin cytoskeleton of cancer cells, impairing the migration in cancer but not in non-cancer cells. We propose that thin GO sheets act as a cue upon interaction with the plasma membrane of cancer cell lines, subsequently inducing actin filaments disruption leading to impaired endocytosis, migration activity, and reduced capacity of cancer cells towards GO uptake.
了解氧化石墨烯（GO）与细胞的相互作用方式对于其安全有效的生物医学应用至关重要。尽管已进行了广泛研究，但仍缺乏使用一组细胞系、经过充分表征的无标记纳米材料以及互补分析技术的系统研究。在此，我们使用共聚焦显微镜、透射电子显微镜和流式细胞术，研究了13种细胞系中具有不同横向尺寸的薄氧化石墨烯片的摄取情况，其中包括8种癌细胞系（HeLa、A549、PC3、DU - 145、LNCaP、SW - 480、SH - SY5Y、U87 - MG）和5种非癌细胞系（BEAS - 2B、NIH/3T3、PNT - 2、HaCaT、293T）。我们的结果揭示了氧化石墨烯摄取方面的显著差异：非癌细胞有效地内化了氧化石墨烯，而在癌细胞中，氧化石墨烯主要与质膜相互作用，内化程度极低或几乎没有内化。与其他纳米材料（聚苯乙烯珠和石墨烯薄片）的比较证实，癌细胞摄取材料的方式与非癌细胞类似，表明存在氧化石墨烯特异性相互作用。我们发现氧化石墨烯的薄度在这种差异摄取中起重要作用。更重要的是，氧化石墨烯会破坏癌细胞的肌动蛋白细胞骨架，损害癌细胞的迁移能力，但对非癌细胞没有影响。我们提出，薄氧化石墨烯片与癌细胞系的质膜相互作用时会起到一种信号作用，随后诱导肌动蛋白丝破坏，导致内吞作用受损、迁移活性降低以及癌细胞摄取氧化石墨烯的能力下降。
