Cationic PAMAM dendrimers disrupt key platelet functions

University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA.
University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA.
University of Utah. Nano Institute of Utah. Program in Molecular Medicine. Salt Lake City, UT, USA.
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.
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.
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.
Thrombodyne, Inc..Salt Lake City, UT, USA.
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.
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.
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.
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.
University of Utah School of Medicine. Department of Pharmaceutics and Pharmaceutical Chemistry. Salt Lake City, UT, USA.
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..

Resumen en ingles

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.

Palabras clave en portugues

Nanotoxicidade
Biocompatibilidade
Ativação plaquetária
Geração de trombina
Dendrímeros

Palabras clave en ingles

nanotoxicity
PAMAM dendrimers
platelet activation
biocompatibility
thrombin generation

Editor

American Chemical Society

Referencia

JONES, Clinton F. et al. Cationic PAMAM dendrimers disrupt key platelet functions. Mol Pharm., v. 9, n.6, p.1599–1611, June 2012.

DOI

10.1021/mp2006054

ISSN

1543-8384

Por favor, use este identificador para citar o enlazar este ítem: https://www.arca.fiocruz.br/handle/icict/23022

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2030-01-01

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