Journal
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Volume 72, Issue -, Pages 201-208Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2017.01.004
Keywords
Dendrimer; PEG; Folic acid; Molecular dynamics; Folate receptor; Drug delivery system
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Funding
- Fraunhofer Chile Research Foundation
- Consejo Nacional de Ciencia y Tecnologia (CONACYT)
- universities Center of Bioinformatics and Molecular Biology (Universidad Andres Bello, Santiago, Chile),
- Centro de Biotecnologia FEMSA
- RED CYTED [214RT0482]
- Scholarship and CONICYT + PAI/Concurso Nacional Tesis de Doctorado en la Empresa 2014 [781413007]
- Chile Research, and Innova-Chile CORFO [FCR-CSB 09CEII-6991]
- Millennium Scientific Initiative of the Ministerio de Economia, Fomento y Turismo
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Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-alpha) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-alpha. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-alpha than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies. (C) 2017 Elsevier Inc.
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