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Published on: November 21, 2016
Low Concentrations of Cationic PAMAM Dendrimers Affect Lymphocyte Respiration in In vitro Studies
Magdalena Labieniec-Watala1, Marzena Szwed, Joanna Hertel
1Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz. Poland.
Background:
In this study, the effect of low concentrations of poly(amido)amine dendrimers (G2-G4) on human lymphocytes was studied. Some works revealed that PAMAMs can adversely affect the morphology of blood components and mitochondria functions. In this context, the present report aimed to investigate the in vitro cationic dendrimers' effect on mitochondrial respiration and cell morphology in lymphocytes isolated from human blood.
Methods:
To monitor the mitochondrial changes, the high-resolution respirometer was used, whereas the cell morphology was analyzed using a flow cytometer and fluorescence microscopy.
Results:
The concentration-dependent dendrimers' influence on lymphocytes morphology was shown. Changes in mitochondrial respiration revealed the concentration- and generation-dependent differences between dendrimer activity. There were no alterations in the routine respiration and in the state of the inner mitochondrial membrane (L/E), but decreased ADP- and FCCP-stimulated respirations were detected after treatment with G3 and G4 dendrimers. The markers of mitochondrial membrane integrity (RCR) and OXPHOS efficiency (P/E) significantly decreased regardless of the dendrimer generation used.
Conclusion:
Based on these in vitro evaluations, we state that cationic PAMAM dendrimers can impair both the morphology and the bioenergetics of human lymphocytes, even when used at low concentrations and in a short time (up to 1 h). However, these results do not imply that similar findings could be possible for in vivo observations.
Insights
Low concentrations of poly(amido)amine dendrimers (PAMAMs) impact human lymphocyte morphology and mitochondrial respiration. These cationic dendrimers impair cell bioenergetics and mitochondrial membrane integrity in vitro.
Area of Science:
- Nanotechnology
- Cell Biology
- Toxicology
Background:
- Poly(amido)amine dendrimers (PAMAMs) may affect blood cell morphology and mitochondrial function.
- Previous research indicates potential adverse effects of PAMAMs on cellular components.
Purpose of the Study:
- To investigate the in vitro effects of cationic PAMAM dendrimers (G2-G4) on human lymphocyte morphology.
- To assess the impact of PAMAMs on mitochondrial respiration in isolated human lymphocytes.
Main Methods:
- High-resolution respirometry was employed to monitor mitochondrial respiration.
- Flow cytometry and fluorescence microscopy were utilized for cell morphology analysis.
Main Results:
- PAMAMs demonstrated a concentration-dependent effect on lymphocyte morphology.
- Mitochondrial respiration showed concentration- and generation-dependent changes, with decreased ADP- and FCCP-stimulated respiration for G3 and G4.
- Mitochondrial membrane integrity (RCR) and OXPHOS efficiency (P/E) were significantly reduced across all PAMAM generations.
Conclusions:
- Cationic PAMAM dendrimers impair human lymphocyte morphology and bioenergetics in vitro, even at low concentrations and short exposure times.
- Observed in vitro effects do not necessarily predict in vivo outcomes.
