(161l) Theophylline-Selective Riboswitch for the Controlled Release of Intercalated Daunomycin
AIChE Annual Meeting
Tuesday, November 16, 2021 - 10:30am to 12:00pm
In the pursuit of an intelligent drug delivery vehicle for cancer therapy, the biomimetic approach - especially using nucleic acid constructs â provides numerous potential carriers with a variety of functionality. Riboswitches are RNA sequences which contain two functional domains, one containing an aptamer for recognition and an effector domain which will alter its double-stranded conformation upon specific molecular interaction with the aptamer. The in vivo functionality of such structures is to control mRNA translation, usually through the exposure or shielding of the Shrine-Dalgarno sequence. The decreasing cost and increasing efficiency in synthesizing biomimetic RNA has opened an enormous toolbox for molecular recognition and controlled release. In this paper, the release of chemotherapeutic and nucleic acid intercalator, daunomycin, from a known theophylline-selective riboswitch is examined using spectral analysis of drug release, calorimetry measurements, and dialysis membrane studies. In the presence of theophylline, molecular interactions with its recognition domain triggers daunomycin to be released from the hairpin structure of the riboswitch through molecular rearrangement. This shift in conformation creates an orientation which has fewer base pairs and therefore fewer locations for daunomycin to intercalate, leading to a rapid release of chemotherapy drug. We expect that this technology can one day be incorporated into nucleic acid nanoparticles as a bioresponsive element for the selective delivery and release of chemotherapy.