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Nanomaterials are promising diagnostic and therapeutic tools for in vivo applications, such as drug delivery, medical imaging and tissue engineering. Dendrimers are being used in numerous biomedical applications, such as gene and antisense therapy, chemotherapy, drug delivery, in vivo diagnostics, and also as anti-infective agents. This article reports novel results about nanotoxicological and teratogenic effects of the PAMAM dendrimers DG4 and DG4.5 in zebrafish (Danio rerio). The objective was to provide a more comprehensive and predictive developmental toxicity screening of DG4 and DG4.5 and test the influence of their surface charge.

Materials And Methods:

Larvae were exposed to dendrimers at 4 dpf and locomotor activity was measured at 4, 24, 48 and 72 hpi (4, 5, 6 and 7 dpf). Activity events were recorded for 15 min at room temperature with an automated system (WMicrotracker) Also, the 50% of the locomotor activity (LAC50) was determined asthe concentration that reduces by half the swimming activity respect to the control.

Results:

Measurement of the locomotor activity allows the prediction of neurotoxic effects in zebrafish larvae. High or low activity respect to the control could be indicative of adverse effects on one or more components of the complex neuronal network that governs the early locomotor system Therefore, alterations in spontaneous locomotor activity are related to the neurotoxicity of the dendrimers. DG4 0.5 μM induced a decrease in the swimming activity of larva at 4, 24, 48 and 72 hpi, and the LAC50 was 0.485, 0.421 and 0.5 μM, respectively (Fig. 2). On the other hand, since DG4.5 caused no alterations in the swimming activity at any of the concentrations tested, LAC50 could not be determined (Fig. 2). Although there is no evidence of the effects on the swimming activity of free DG4 and DG4.5 in zebrafish larvae, it has been reported that DG4 has a concentration and time-dependent toxicity in zebrafish embryos, which correlates with the effect observed with this dendrimer in larval activity.

Nanotoxicological and teratogenic effects: A linkage between dendrimer surface charge and zebrafish developmental stages.

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Toxicol Appl Pharmacol. 2017 Dec 15;337:1-11. doi: 10.1016/j.taap.2017.10.003. Epub 2017 Oct 7.

Calienni MN, Feas DA, Igartúa DE, Chiaramoni NS, Alonso SDV, Prieto MJ.

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