Differences in the Cell Type-Specific Toxicity of Diamond Nanoparticles to Endothelial Cells Depending on the Exposure of the Cells to Nanoparticles

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2023 Jun 5

PMID 37273285

Authors

Mateusz Wierzbicki

Katarzyna Zawadzka

Barbara Wojcik

Slawomir Jaworski

Barbara Strojny

Agnieszka Ostrowska

Artur Malolepszy

Marta Mazurkiewicz-Pawlicka

Ewa Sawosz

Affiliations

Soon will be listed here.

Abstract

Introduction: Diamond nanoparticles are considered to be one of the most cytocompatible carbon nanomaterials; however, their toxicity varies significantly depending on the analysed cell types. The aim was to investigate the specific sensitivity of endothelial cells to diamond nanoparticles dependent on exposure to nanoparticles.

Methods: Diamond nanoparticles were characterized with Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS). Toxicity of diamond nanoparticles was assessed for endothelial cells (HUVEC), human mammary epithelial cells (HMEC) and HS-5 cell line. The effect of diamond nanoparticles on the level of ROS, NO, NADPH and protein synthesis of angiogenesis-related proteins of endothelial cells was evaluated.

Results And Discussion: Our studies demonstrated severe cell type-specific toxicity of diamond nanoparticles to endothelial cells (HUVEC) depending on nanoparticle surface interaction with cells. Furthermore, we have assessed the effect on cytotoxicity of the bioconjugation of nanoparticles with a peptide containing the RGD motive and a serum protein corona. Our study suggests that the mechanical interaction of diamond nanoparticles with the endothelial cell membranes and the endocytosis of nanoparticles lead to the depletion of NADPH, resulting in an intensive synthesis of ROS and a decrease in the availability of NO. This leads to severe endothelial toxicity and a change in the protein profile, with changes in major angiogenesis-related proteins, including VEGF, bFGF, ANPT2/TIE-2, and MMP, and the production of stress-related proteins, such as IL-6 and IL-8.

Conclusion: We confirmed the presence of a relationship between the toxicity of diamond nanoparticles and the level of cell exposure to nanoparticles and the nanoparticle surface. The results of the study give new insights into the conditioned toxicity of nanomaterials and their use in biomedical applications.

Citing Articles

A Comprehensive Assessment of the Biocompatibility and Safety of Diamond Nanoparticles on Reconstructed Human Epidermis.

Fraczek W, Kregielewski K, Wierzbicki M, Krzeminski P, Zawadzka K, Szczepaniak J Materials (Basel). 2023; 16(16).

PMID: 37629892 PMC: 10456456. DOI: 10.3390/ma16165600.

References

Zakrzewska K, Samluk A, Wierzbicki M, Jaworski S, Kutwin M, Sawosz E . Analysis of the cytotoxicity of carbon-based nanoparticles, diamond and graphite, in human glioblastoma and hepatoma cell lines. PLoS One. 2015; 10(3):e0122579. PMC: 4376528. DOI: 10.1371/journal.pone.0122579. View

Mollnau H, Wendt M, Szocs K, Lassegue B, Schulz E, Oelze M . Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res. 2002; 90(4):E58-65. DOI: 10.1161/01.res.0000012569.55432.02. View

Lassegue B, San Martin A, Griendling K . Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res. 2012; 110(10):1364-90. PMC: 3365576. DOI: 10.1161/CIRCRESAHA.111.243972. View

Shi J, Sun X, Lin Y, Zou X, Li Z, Liao Y . Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-κB pathways. Biomaterials. 2014; 35(24):6657-66. DOI: 10.1016/j.biomaterials.2014.04.093. View

Burtenshaw D, Hakimjavadi R, Redmond E, Cahill P . Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate. Antioxidants (Basel). 2017; 6(4). PMC: 5745500. DOI: 10.3390/antiox6040090. View

Chauhan S, Jain N, Nagaich U . Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents. J Pharm Anal. 2020; 10(1):1-12. PMC: 7037532. DOI: 10.1016/j.jpha.2019.09.003. View

Chithrani B, Chan W . Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Lett. 2007; 7(6):1542-50. DOI: 10.1021/nl070363y. View

Chen F, Kumar S, Yu Y, Aggarwal S, Gross C, Wang Y . PKC-dependent phosphorylation of eNOS at T495 regulates eNOS coupling and endothelial barrier function in response to G+ -toxins. PLoS One. 2014; 9(7):e99823. PMC: 4096401. DOI: 10.1371/journal.pone.0099823. View

Liton P, Luna C, Bodman M, Hong A, Epstein D, Gonzalez P . Induction of IL-6 expression by mechanical stress in the trabecular meshwork. Biochem Biophys Res Commun. 2005; 337(4):1229-36. PMC: 3152460. DOI: 10.1016/j.bbrc.2005.09.182. View

10.

Cheng H, Zhong W, Wang L, Zhang Q, Ma X, Wang Y . Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches. Biomed Pharmacother. 2023; 158:114198. DOI: 10.1016/j.biopha.2022.114198. View

11.

Akwii R, Sajib M, Zahra F, Mikelis C . Role of Angiopoietin-2 in Vascular Physiology and Pathophysiology. Cells. 2019; 8(5). PMC: 6562915. DOI: 10.3390/cells8050471. View

12.

Huang Y, Cambre M, Lee H . The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms. Int J Mol Sci. 2017; 18(12). PMC: 5751303. DOI: 10.3390/ijms18122702. View

13.

Godbole A, Lu X, Guo X, Kassab G . NADPH oxidase has a directional response to shear stress. Am J Physiol Heart Circ Physiol. 2008; 296(1):H152-8. PMC: 2637776. DOI: 10.1152/ajpheart.01251.2007. View

14.

Yin S, Liu J, Kang Y, Lin Y, Li D, Shao L . Interactions of nanomaterials with ion channels and related mechanisms. Br J Pharmacol. 2019; 176(19):3754-3774. PMC: 6780043. DOI: 10.1111/bph.14792. View

15.

Garriga R, Herrero-Continente T, Palos M, Cebolla V, Osada J, Munoz E . Toxicity of Carbon Nanomaterials and Their Potential Application as Drug Delivery Systems: In Vitro Studies in Caco-2 and MCF-7 Cell Lines. Nanomaterials (Basel). 2020; 10(8). PMC: 7466705. DOI: 10.3390/nano10081617. View

16.

Frohlich E . The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012; 7:5577-91. PMC: 3493258. DOI: 10.2147/IJN.S36111. View

17.

Fang Y, Eglen R . Three-Dimensional Cell Cultures in Drug Discovery and Development. SLAS Discov. 2017; 22(5):456-472. PMC: 5448717. DOI: 10.1177/1087057117696795. View

18.

Kopac T . Protein corona, understanding the nanoparticle-protein interactions and future perspectives: A critical review. Int J Biol Macromol. 2020; 169:290-301. DOI: 10.1016/j.ijbiomac.2020.12.108. View

19.

Gray K, Stroka K . Vascular endothelial cell mechanosensing: New insights gained from biomimetic microfluidic models. Semin Cell Dev Biol. 2017; 71:106-117. DOI: 10.1016/j.semcdb.2017.06.002. View

20.

Li J, Zhu Y, Li W, Zhang X, Peng Y, Huang Q . Nanodiamonds as intracellular transporters of chemotherapeutic drug. Biomaterials. 2010; 31(32):8410-8. DOI: 10.1016/j.biomaterials.2010.07.058. View