Other Pharmacology, Toxicology and Environmental Health Commons^™

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells, …

Generation Of Intracellular Reactive Oxygen Species And Genotoxicity Effect To Exposure Of Nanosized Polyamidoamine (Pamam) Dendrimers In Plhc-1 Cells In Vitro, Hugh Byrne, Pratap Naha

Articles

Polyamidoamine (PAMAM) dendrimers elicit systematically variable cyto- and eco-toxic responses, promising the basis for structure activity relationships governing nanotoxicological responses. Increased production of intracellular reactive oxygen species (ROS), genotoxicity and apoptosis due to in-vitro exposure of hepatocellular carcinoma cells to dendrimer generations G-4, G-5 and G-6 is demonstrated. A generation dependent increase in ROS and genotoxicity was observed, consistent with our previous studies. The responses correlate well with the number of surface amino groups per generation. Although ROS production initially increases approximately linearly, it saturates at higher doses. Notably, normalised to molar dose of surface amino groups, the dose-dependent ROS …