Cationic PAMAM dendrimers disrupt key platelet functions
| Autor: | Christopher C. Gibson, Andrew S. Weyrich, S. Fazal Mohammad, Benjamin D. Brooks, Dean Y. Li, David W. Grainger, Zechariah Franks, Sivaprasad Sukavaneshvar, Adriana Vieira-de-Abreu, Giridhar Thiagarajan, Robert A. Campbell, Clinton F. Jones, Hamidreza Ghandehari |
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| Rok vydání: | 2012 |
| Předmět: |
Blood Platelets
Dendrimers Biocompatibility Platelet Function Tests Pharmaceutical Science Nanoparticle Nanotechnology Article Thrombin Dendrimer Drug Discovery medicine Humans Platelet Platelet activation Cells Cultured Microscopy Confocal Chemistry Flow Cytometry Platelet Activation In vitro Nanotoxicology Biophysics Molecular Medicine Nanoparticles medicine.drug |
| Zdroj: | Molecular pharmaceutics. 9(6) |
| ISSN: | 1543-8392 |
| Popis: | Poly(amidoamine) (PAMAM) dendrimers have been proposed for a variety of biomedical applications and are increasingly studied as model nanomaterials for such use. The dendritic structure features both modular synthetic control of molecular size and shape and presentation of multiple equivalent terminal groups. These properties make PAMAM dendrimers highly functionalizable, versatile single-molecule nanoparticles with a high degree of consistency and low polydispersity. Recent nanotoxicological studies showed that intravenous administration of amine-terminated PAMAM dendrimers to mice was lethal, causing a disseminated intravascular coagulation-like condition. To elucidate the mechanisms underlying this coagulopathy, in vitro assessments of platelet functions in contact with PAMAM dendrimers were undertaken. This study demonstrates that cationic G7 PAMAM dendrimers activate platelets and dramatically alter their morphology. These changes to platelet morphology and activation state substantially altered platelet function, including increased aggregation and adherence to surfaces. Surprisingly, dendrimer exposure also attenuated platelet-dependent thrombin generation, indicating that not all platelet functions remained intact. These findings provide additional insight into PAMAM dendrimer effects on blood components and underscore the necessity for further research on the effects and mechanisms of PAMAM-specific and general nanoparticle toxicity in blood. |
| Databáze: | OpenAIRE |
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