title: Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.
abstract: Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) 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-α. 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-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies.
authors.affiliation: Centro de Biotecnología FEMSA, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Col. Tecnológico, Monterrey, N.L, Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Sampogna-Mireles
authors.affiliation: Universidad Andres Bello, Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biológicas, Av. República 239, Santiago, Chile.
authors.forename: Ingrid D
authors.initials: ID
authors.lastname: Araya-Durán
authors.affiliation: Universidad Andres Bello, Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biológicas, Av. República 239, Santiago, Chile; Fundación Fraunhofer Chile Research, M. Sanchez Fontecilla 310, Las Condes, Chile.
authors.forename: Valeria
authors.initials: V
authors.lastname: Márquez-Miranda
authors.affiliation: Centro de Biotecnología FEMSA, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Col. Tecnológico, Monterrey, N.L, Mexico. Electronic address: valencia@itesm.mx.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Valencia-Gallegos
authors.affiliation: Universidad Andres Bello, Center for Bioinformatics and Integrative Biology (CBIB), Facultad de Ciencias Biológicas, Av. República 239, Santiago, Chile; Fundación Fraunhofer Chile Research, M. Sanchez Fontecilla 310, Las Condes, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile. Electronic address: fernando.gonzalez@unab.cl.
authors.forename: Fernando D
authors.initials: FD
authors.lastname: González-Nilo
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D058975:Folate Receptor 1 / Q000737:chemistry* / Q000378:metabolism*; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D050091:Dendrimers; D058975:Folate Receptor 1; D012997:Solvents; D011092:Polyethylene Glycols; D005492:Folic Acid
keywords: Dendrimer; Drug delivery system; Folate receptor; Folic acid; Molecular dynamics; PEG