Premium
Structural dependence of in vitro cytotoxicity, oxidative stress and uptake mechanisms of poly(propylene imine) dendritic nanoparticles
Author(s) -
Khalid Humza,
Mukherjee Sourav Prasanna,
O'Neill Luke,
Byrne Hugh J.
Publication year - 2016
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3267
Subject(s) - cytotoxicity , dendrimer , biophysics , intracellular , cytotoxic t cell , hacat , oxidative stress , confocal microscopy , chemistry , nanotoxicology , keratinocyte , in vitro , microbiology and biotechnology , biochemistry , biology , toxicity , organic chemistry
The in vitro cytotoxic and intracellular oxidative stress responses to exposure to poly(propylene imine) (PPI) dendritic nanoparticles of increasing generation (number of repeated branching cycles) (G0–G4) were assessed in an immortal non‐cancerous human keratinocyte cell line (HaCaT). Confocal fluorescence microscopy with organelle staining was used to explore the uptake and intracellular trafficking mechanisms. A generation‐ and dose‐dependent cytotoxic response was observed, increasing according to generation and, therefore, number of surface amino groups. A comparison of the cytotoxic response of G4 PPI and the related G4 poly(amido amine) dendrimer indicates that the PPI with the same number of surface amino groups elicits a significantly higher cytotoxic response. The trend of cytotoxicity versus dendrimer generation and, therefore, size is discontinuous in the region of G2, however, indicating a difference in uptake mechanism for higher compared to lower generations. Whereas the higher generations elicit an oxidative stress response at short exposure times, the lower generations indicate an antioxidant response. Confocal microscopy indicates that, whereas they are prominent at early exposure times for the larger PPI dendrimers, no evidence of early stage endosomes was observed for lower generations of PPI. The results are consistent with an alternative uptake mechanism of physical diffusion across the semipermeable cell membrane for the lower generation dendrimers and are discussed in terms of their implications for predictive models for nanotoxicology and design strategies for nanomedical applications. Copyright © 2015 John Wiley & Sons, Ltd.