Abstract
Doxorubicin (DOX) is a commonly employed drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of promising DOX-loaded DNA nanocarriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures. In our experimental conditions, all of our DNA origami designs show similar DOX binding capacities, which are, however, remarkably lower than previously reported. To simulate the possible physiological degradation pathways, we examine the stability and DOX release properties of the complexes upon DNase I digestion, revealing customizable drug release profiles related to the DNA origami superstructure and the loaded DOX content. In addition, we identify major DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration that have been largely ignored in experimenting with DNA nanostructures. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA carriers.
Competing Interest Statement
The authors have declared no competing interest.