The intracellular trafficking and delivery of nucleic acids in cells is a field of growing interest both from a fundamental standpoint and for therapeutic applications. Spectroscopic methods can be used to observe and quantitatively measure the extent of delivery of therapeutically active oligonucleotides both in vitro and in vivo. Here we present novel chemical design elements into a newly developed hybrid biomaterial called nucleic acid nanocapsule (NAN). These new modifications consist of optically activatable cross-linkers and fluorophore labeled surfactants that can be used for monitoring the trafficking of therapeutic nucleic acids (TNAs) in the cell.  These new cross-linkers contain nitro-phenol cross-linkages that are incorporated into the NANs surface. Upon degradation of the NAN by enzymes, the extent of disassembly can be monitored spectroscopically due to the production of phenol ions. In a second parallel approach a fluorophore-labeled surfactant consisting of a solvatochromatic chromophore is present which can be utilized to track the movement of a surfactant-nucleic acid conjugate using a fluorescently labeled oligonucleotide cargo. Using these new chemical probes tailored to the NANs assembly and disassembly, mechanistic insights into the stability and degradation of NANs both in vitro and in cell culture can be studied effectively, providing new tools that will allow us to measure the cellular uptake, stability and trafficking of TNA conjugates intracellularly in real time.

Monitoring cellular trafficking of therapeutic nucleic acids in the real-time

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.