A variety of nanoscale synthetic non-viral carriers have been developed for nucleic acid delivery. Recently, combination therapies have begun to explore the co-delivery of nucleic acids and proteins. Our laboratory has developed a unique DNA crosslinked micelle which we refer to as a nucleic acid nanocapsule (NAN) that we have previously utilized for the successful intracellular delivery of short oligonucleotides (less than 40 bases long) coupled with hydrophobic small molecule dyes and drugs. Here we detail a new DNA micelle design that can enable the co-encapsulation of larger more hydrophilic cargo, including plasmids and proteins. We explore the synthesis of hybrid nanoscale designs and chemical triggers within this structure, including the development of a metal organic framework-micelle assembly and a thermoresponsive crosslinker. We show studies in which we can use various stimuli (pH, enzymes) to regulate access of the MOF-micelles cargo to its environment and the overall degradation properties of the construct. We show that these assemblies and chemistries enable encapsulation of larger biomacromolecules and that these hybrid systems result in a wider array of release triggers, including a pH responsive zeolite MOF delivery platform – a promising alternative to the premature degradation and limitations of traditional MOFs for intracellular delivery applications.

Expanding the chemistry and cargo compatibility of DNA-micelle delivery systems

ACS Fall 2021

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