Supramolecular-mediated dual-functional DNA nanocomposites for programmable cancer therapy

Programmable cancer therapies may perfectly prevent mutual drug restrictions, however, developing an efficient codelivery system with such an ability remains challenging. We herein first demonstrate the use of supramolecular-mediated dual-functional DNA nanocomposites for programmable chemodynamic therapy (CDT) and chemotherapy (CT), in which a water-soluble cyclodextrin-resveratrol (CD-Res) complex can be facilely encapsulated during the coassembly of Fe²⁺ and DNA to form the desired spherical nanocomposites. After endocytosis, the released Fe²⁺ can immediately trigger an endogenous Fenton reaction, inducing ferroptosis for CDT and ˙OH depletion, followed by the sustained release of the protected Res from the CD cavity. This process improves the efficacy of CT by preventing Res from the oxidation of ˙OH. The as-prepared nano-composites can sufficiently accumulate in the tumor, demonstrating an adequate programmable therapeutic performance without serious toxicity. Thus, a facile, fresh and changeable strategy for the design of antitumor therapies is presented.