DNA Binding on Self-Assembled Monolayers Terminated with Mixtures of Ammonium and Trimethylammonium Groups: Toward a Gene-Delivery Platform

The formation of binary self-assembled monolayers (SAMs) via the use of ammonium-terminated adsorbates offers an ionic platform for the binding of oligonucleotides and their subsequent delivery for therapeutic applications. Four different types of ammonium-terminated adsorbates were used in the present study: two ammonium-terminated and two trimethylammonium-terminated dithiols of different chain lengths, which were designed to provide a foundation for the development of a high-capacity nanoscale loading system for oligonucleotides. The maximum number of oligonucleotides immobilized on the surface was achieved by adjusting the ratio of the adsorbates in correlation with the relative packing density of the SAMs. The techniques of ellipsometry, X-ray photoelectron spectroscopy, polarization modulation infrared reflection-absorption spectroscopy, and electrochemical quartz crystal microbalance were used to analyze the SAMs. Analysis of the films revealed an optimum ratio of 75:25 of the long-chained adsorbate (ammonium-terminated) to the short-chained adsorbate (trimethylammonium-terminated) for maximum oligonucleotide loading. Further analysis indicated that burying the trimethylammonium termini into the lower interface of the monolayer provided the highest mass loading of oligonucleotides. The results presented in this study provide a foundation for the development of a gene-therapy platform when constructed on the surface of, for example, light-responsive gold nanoparticles or gold nanoshells as photo-triggerable delivery vehicles.