title: Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers.
abstract: Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers.
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Santiago, Chile; Fundación Fraunhofer Chile Research, Las Condes, Chile.
authors.forename: Valeria
authors.initials: V
authors.lastname: Márquez-Miranda
authors.affiliation: Universidad Bernardo O Higgins, Laboratorio de Bionanotecnología, Santiago, Chile.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Camarada
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Santiago, Chile; Fundación Fraunhofer Chile Research, Las Condes, Chile.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Araya-Durán
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Santiago, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varas-Concha
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Santiago, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Daniel Eduardo
authors.initials: DE
authors.lastname: Almonacid
authors.affiliation: Universidad Andres Bello, Facultad de Biología, Center for Bioinformatics and Integrative Biology (CBIB), Santiago, Chile; Fundación Fraunhofer Chile Research, Las Condes, Chile; Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
authors.forename: Fernando Danilo
authors.initials: FD
authors.lastname: González-Nilo
mesh_terms: D032701:Biomimetics; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry*; D018014:Gene Transfer Techniques; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst