Low Dose of Amino-Modified Nanoparticles Induces Cell Cycle Arrest

Abstract

The interaction of nanoscaled materials with biological systems is currently the focus of a fast-growing area of investigation. Though many nanoparticles interact with cells without acute toxic responses, amino-modified polystyrene nanoparticles are known to induce cell death. We have found that by lowering their dose, cell death remains low for several days while, interestingly, cell cycle progression is arrested. In this scenario, nanoparticle uptake, which we have recently shown to be affected by cell cycle progression, develops differently over time due to the absence of cell division. This suggests that the same nanoparticles can trigger different pathways depending on exposure conditions and the dose accumulated.

High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles

“…Before the nanoparticles were exposed to the selected cell lines we verified the dispersion characteristics of the NPs utilized. PS-NH 2 and PS-COOH NPs have been extensively characterised and have shown to be very stable once dispersed in cell culture medium, showing negligible agglomeration [42]–[44]. NPs physico-chemical properties were assessed by Dynamic Light Scattering (DLS) after diluting the commercial dispersion in reference buffers (10 mM NaCl and PBS) as well as the complete cell culture medium supplemented with 10% fetal bovine serum (FBS) used to grow the cell cultures, in order to assess whether the effective dose presented to the cells was consistent with the applied dose.…”

A guide to nanosafety testing: Considerations on cytotoxicity testing in different cell models

“…The aim of our study was to investigate the applicability of three cytotoxicity assays in a variety of different cell models representing the most important target organs for NPs. Amine-modified polystyrene NPs (PS-NH 2 ) and carboxyl-modified polystyrene NPs (PS-COOH) were used as 'model' NPs as they exhibit narrow size ranges and low agglomeration (Bexiga et al 2014;Kim et al 2013;Wang et al 2013). Moreover, the cationic PS-NH 2 have been demonstrated to induce cytotoxicity at doses below 50 g/ml (Anguissola et al 2014;Bexiga et al 2011;Ruenraroengsak et al 2012;Wang et al 2013;Xia et al 2008).…”

Transient loading of CD34⁺ hematopoietic progenitor cells with polystyrene nanoparticles

“…As NPs are of the same order of magnitude as biomolecules and viruses, they are capable of entering the cells and interact with the cellular machinery. 6,7 In the medical field, NP-based strategies offering unprecedented applications are therefore increasingly preferred over the traditional diagnostic and therapeutic methods. Indeed, 1) NPs can easily be loaded with imaging agents, bioactive molecules and drugs due to their large surface area and inner volume, 2) NP surfaces can be easily functionalized and as such have the possibility to allow for specific (sub)cellular targeting, 3) NPs display an enhanced circulation time in the blood compared to traditional therapeutics, and 4) NPs can be made multifunctional to exert both diagnostic and therapeutic actions.…”