AVS 62nd International Symposium & Exhibition | |
Biomaterial Interfaces | Tuesday Sessions |
Session BI-TuP |
Session: | Biomaterial Interfaces Poster Session |
Presenter: | Michael Newton, University of Washington |
Authors: | M.A. Newton, University of Washington J.M. Carothers, University of Washington D.G. Castner, University of Washington |
Correspondent: | Click to Email |
Gold nanoparticles (AuNPs) promise to offer a minimally toxic, easily modifiable, and high payload carrying drug or biologic delivery agent. Despite this promise and the emphasis placed on their intrinsically high surface area to volume ratio, surface functionalized AuNP conjugates in biomedical applications often lack detailed surface characterization. Consequently, there is little experimental validation of a surface attached ligand’s orientation or conformation. Nucleic acids are one such ligand and biologic diagnostic or therapeutic agent currently being investigated. RNA-based logic circuits responsive to small molecules, endogenous proteins, and miRNAs have been demonstrated to diagnose the state of a cell and implement a programmed therapeutic outcome. A truncated RNA circuit such as this could benefit from local targeting and concentrated delivery on a nanoparticle platform and prove more effective. Proper tools and techniques to characterize biomedical AuNP conjugates would inform their design and result in better understanding the observed cellular uptake, efficacy, toxicity, and clearance.
Short single-stranded DNA oligo’s on AuNPs have been used to sense a complementary nucleic acid, or as a capture strand to facilitate assembly of larger constructs. Additionally it is often recognized that the method of attachment and incorporation of spacers will play a factor in the assembled conjugate’s performance. A thiol attachment to Au is often used with a polynucleotide spacer for simple assembly and increased performance. These investigations typically neglect to consider other types of spacers like ethylene glycol chains of various lengths. We will compare the polynucleotide and ethylene glycol spacers used individually and jointly in a single-stranded DNA capture oligo conjugated AuNP in terms of particle surface characterization and nucleic acid functionality. This will be realized through X-ray Photoelectron Spectroscopy and Localized Surface Plasmon Resonance in conjunction with standard bulk characterizations like Dynamic Light Scattering, Electrophoresis, and Transmission Electron Microscopy, and through incorporation of strand-displacement and RNA aptamer nucleic acid devices with distinct programmed fluorescent outputs from a specific small molecule or oligo input.