Supramolecular Nucleoside-Based Gel: Molecular Dynamics Simulation and Characterization of Its Nanoarchitecture and Self-Assembly Mechanism

• Published in: Langmuir 2018-06, Vol.34 (23), p.6912-6921
• Main Authors: Angelerou, Maria G. F, Frederix, Pim W. J. M, Wallace, Matthew, Yang, Bin, Rodger, Alison, Adams, Dave J, Marlow, Maria, Zelzer, Mischa
• Format: Article
• Language: English
• Subjects: biocompatibility; biopharmaceuticals; Drug Delivery Systems - methods; encapsulation; hydrogels; Hydrogels - chemical synthesis; Hydrogels - chemistry; Hydrophobic and Hydrophilic Interactions; hydrophobicity; molecular dynamics; Molecular Dynamics Simulation; nanomaterials; nucleic acids; proteins; tissue engineering; Tissue Engineering - methods
• ISSN: 0743-7463; 1520-5827; 1520-5827
• DOI: 10.1021/acs.langmuir.8b00646

Among the diversity of existing supramolecular hydrogels, nucleic acid-based hydrogels are of particular interest for potential drug delivery and tissue engineering applications because of their inherent biocompatibility. Hydrogel performance is directly related to the nanostructure and the self-assembly mechanism of the material, an aspect that is not well-understood for nucleic acid-based hydrogels in general and has not yet been explored for cytosine-based hydrogels in particular. Herein, we use a broad range of experimental characterization techniques along with molecular dynamics (MD) simulation to demonstrate the complementarity and applicability of both approaches for nucleic acid-based gelators in general and propose the self-assembly mechanism for a novel supramolecular gelator, N 4-octanoyl-2′-deoxycytidine. The experimental data and the MD simulation are in complete agreement with each other and demonstrate the formation of a hydrophobic core within the fibrillar structures of these mainly water-containing materials. The characterization of the distinct duality of environments in this cytidine-based gel will form the basis for further encapsulation of both small hydrophobic drugs and biopharmaceuticals (proteins and nucleic acids) for drug delivery and tissue engineering applications.