Simply Designed and Universal DNA Nanohydrogel for Stimuli-Responsive NIR-II Fluorescence Imaging of Early-Stage Tumor.

The delayed detection and recurrence of cancer lead to disappointing cure rates, underscoring the imperative for exploring precise early tumor diagnosis techniques. Despite the superior biocompatibility and flexible programmability of DNA nanoprobes for tumor imaging, intricate designs with multiple oligonucleotide sequences are always indispensable, which significantly hinder their clinical application and commercial development. To construct a simply designed DNA nanoprobe, here, we constructed a universal stimuli-responsive nanohydrogel through the hybridization of the staple strand and skeleton strand. Through a simple substitution of the staple strand, this hydrogel can be adapted for the response to different targets without necessitating a series of subsequent revisions and synthesis optimization. To achieve near-infrared II region (NIR-II) fluorescence imaging, alkynyl-modified NIR-II fluorescent dyes are labeled at two ends of bent staple strands and display weak fluorescence because of the aggregation-caused quenching effect. The highly expressed ATP or cytokine in tumor cells activates the liberation of staples and collapse of the bent configuration, which generates fluorescence recovery for tumor imaging. Moreover, this nanohydrogel also allows for the targeted release of anticancer drugs intercalated in the DNA helix. By integration of NIR-II fluorescent dyes, this versatile nanohydrogel enables precise diagnosis and treatment of early tumors. The straightforward design demonstrates low cost and easy adaptability for multitarget detection, highlighting its significant implications for the advancement of DNA nanotechnology in clinical application and commercialization production.