Author | Jones, Clinton F. | |
Author | Campbell, Robert A. | |
Author | Franks, Zechariah | |
Author | Gibson, Christopher C. | |
Author | Thiagarajan, Giridhar | |
Author | Abreu, Adriana Vieira de | |
Author | Sukavaneshvar, Sivaprasad | |
Author | Mohammad, S. Fazal | |
Author | Li, Dean Y. | |
Author | Ghandehari, Hamidreza | |
Author | Weyrich, Andrew S. | |
Author | Brooks, Benjamin D. | |
Author | Grainger, David W. | |
Access date | 2017-11-01T14:18:33Z | |
Available date | 2017-11-01T14:18:33Z | |
Document date | 2012 | |
Citation | JONES, Clinton F. et al. Cationic PAMAM dendrimers disrupt key platelet functions. Mol Pharm., v. 9, n.6, p.1599–1611, June 2012. | pt_BR |
ISSN | 1543-8384 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/23022 | |
Language | eng | pt_BR |
Publisher | American Chemical Society | pt_BR |
Rights | restricted access | |
Subject in Portuguese | Nanotoxicidade | pt_BR |
Subject in Portuguese | Biocompatibilidade | pt_BR |
Subject in Portuguese | Ativação plaquetária | pt_BR |
Subject in Portuguese | Geração de trombina | pt_BR |
Subject in Portuguese | Dendrímeros | pt_BR |
Title | Cationic PAMAM dendrimers disrupt key platelet functions | pt_BR |
Type | Article | |
DOI | 10.1021/mp2006054 | |
Abstract | 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. | pt_BR |
Affilliation | University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA. / University of Utah. Department of Bioengineering. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Utah Center for Nanomedicine. Salt Lake City, UT, USA / University of Utah. Department of Bioengineering. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Salt Lake City, UT, USA. | pt_BR |
Affilliation | Thrombodyne, Inc..Salt Lake City, UT, USA. | pt_BR |
Affilliation | Thrombodyne, Inc..Salt Lake City, UT, USA. / University of Utah. Department of Patholoogy. Salt Lake City, UT, USA / University of Utah. Utah Artificial Heart Institute, Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA / University of Utah. Department of Internal Medicine. Division of Cardiology. Salt Lake City, UT, USA / University of Utah. Department of Oncological Sciences. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA / University of Utah. Nano Institute of Utah. Utah Center for Nanomedicine. Salt Lake City, UT, USA / University of Utah. Department of Bioengineering. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA / University of Utah. Department of Internal Medicine. Divisions of Pulmonary and Critical Care Medicine. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA. | pt_BR |
Affilliation | University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA / University of Utah. Nano Institute of Utah. Utah Center for Nanomedicine. Salt Lake City, UT, USA / University of Utah. Department of Bioengineering. Salt Lake City, UT, USA.. | pt_BR |
Subject | nanotoxicity | pt_BR |
Subject | PAMAM dendrimers | pt_BR |
Subject | platelet activation | pt_BR |
Subject | biocompatibility | pt_BR |
Subject | thrombin generation | pt_BR |
e-ISSN | 1543-8392 | |
Embargo date | 2030-01-01 | |