Colloids and Surfaces B: Biointerfaces 162 (2018) 380–388 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces jo ur nal ho me p ag e: www.elsevier.com/locate/colsurfb Study of non-covalent interactions on dendriplex formation: Influence of hydrophobic, electrostatic and hydrogen bonds interactions María Sánchez-Milla a,b,c , Isabel Pastor c,d , Marek Maly e , M. Jesús Serramía c,f,g,h , Rafael Gómez a,b,c , Javier Sánchez-Nieves a,b,c,∗ , Félix Ritort c,d , M. Ángeles Mu˜ noz-Fernández c,f,g,h , F. Javier de la Mata a,b,c,∗ a Department of Química Orgánica y Química Inorgánica, Universidad de Alcalá (IRYCIS), Campus Universitario, E-28871 Alcalá de Henares, Madrid, Spain b Instituto de Investigación Química “Andrés M. del Río” (IQAR), Universidad de Alcalá, Spain c Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain d Small Biosystems Lab, Condensed Matter Physics Department, Universitat de Barcelona, C/Martí i Franquès, E-08028, Barcelona, Spain e Faculty of Science, J. E. Purkinje University, Ceske mladeze 8, 400 96 Usti nad Labem, Czech Republic f Sección Inmunología, Laboratorio de InmunoBiología Molecular, Hospital General Universitario Gregorio Mara˜ nón, Madrid, Spain g Instituto de Investigación Sanitaria Gregorio Mara˜ nón, Madrid, Spain h Spanish HIV HGM BioBank, Madrid, Spain a r t i c l e i n f o Article history: Received 5 August 2017 Received in revised form 10 November 2017 Accepted 7 December 2017 Available online 8 December 2017 Keywords: Dendrimers Carbosilane Gene therapy siRNA Molecular dynamics Force spectroscopy a b s t r a c t The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane den- drimers of generations 1–3 with two different ammonium functions at the periphery ([−NMe 2 R] + , R = Me, (CH 2 ) 2 OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the par- ticular case of first generation dendrimer [G 1 O 3 (NMe 2 (CH 2 ) 2 OH)) 6 ] 6+ ; the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Gene therapy is a technique that uses genetic material, such as plasmids, nucleic acids (DNA and RNA) and oligonucleotides, to treat diseases and has become a very attractive research area [1]. However, the aforesaid naked systems are easily degraded and also are unable to penetrate into the cells due to their size and negative charge. To circumvent this problem, gene delivery carriers have been developed. The mission of these vectors is to turn nucleic acid invisible to nucleases and favour the crossing of cell mem- branes. Two types of gene delivery vectors can be distinguished: ∗ Corresponding authors at: Department of Química Orgánica y Química Inorgánica, Universidad de Alcalá (IRYCIS), Campus Universitario, E-28871 Alcalá de Henares, Madrid, Spain E-mail addresses: javier.sancheznieves@uah.es (J. Sánchez-Nieves), javier.delamata@uah.es (F.J. de la Mata). viral and non-viral. Viruses and their modifications show consid- erable disadvantages due to their nature [2,3]. On the other hand, non-viral vectors are synthetic systems, such as macromolecules, polymers and nanosystems, being designed by controlled proce- dures [4–11]. These carriers interact with nucleic acids, usually electrostatically, compacting them and preventing their degrada- tion. For this reason, an important type of nucleic acid vectors are cationic macromolecules [12]. Another important factor in the design of synthetic vectors is the size of the nucleic acid to transfect, from small oligonucleotides to the biggest DNA, requiring bigger delivery systems as the size of the nucleic acid increases. Hence, since cationic systems are toxic, a higher charge number leads to higher toxicity and, therefore, it is desirable to find smaller carriers while keeping an adequate activity. Dendrimers are spherical macromolecules with well-defined size and structure, monodisperse, flexible, and with a multiva- lent molecular surface, that have attracted attention for biomedical applications [13–19]. Several types of cationic dendrimers con- https://doi.org/10.1016/j.colsurfb.2017.12.009 0927-7765/© 2017 Elsevier B.V. All rights reserved.