Plain DNA and cationic aromatics: a platform to simplify carrier-free delivery systems

DNA nanotechnology offers a powerful alternative in biomedical areas yet a simple and general strategy to engineer DNA-based nanomedicine bearing high and adjustable drug-loading capacity and stability remains challenging. Herein, we report that it is a ubiquitous property for plain DNA (except for guanine-rich sequences) to assemble with the widely used anticancer drug, doxorubicin hydrochloride (DOX), into well-defined nanospheres via thermal annealing, which circumvents additional adjuvants (e.g., metal ions) or chemical modifications of DNA (e.g., hydrophobic conjugation). Experimental results and molecular dynamics simulation reveal that shape remolding is a result of heat-promoted intra-particle interactions. We demonstrate that the nanospheres display high DOX-loading capacity and feasible size controllability, and the generality of this approach is also established with diverse functional cationic aromatics (drugs, fluorescent dyes and aggregation-induced emission luminogens). Finally, we construct a carrier-free nanomedicine by assembling DOX with a therapeutic antisense oligonucleotide, and the combined therapeutic performance is demonstrated in vitro and in vivo.