Carrier-free catalyzed hairpin assembly propelled sensing-to-therapy DNA amplifier under a cascaded light-responsive switching

Despite DNA amplifiers own forceful capability for sensing low-abundance analytes in living biosystems, the usage of complicated carriers and the uncontrollable sensing phase make them difficult to collectively conduct therapeutic application. Herein, we expect to overcome these obstacles. For one thing, antisense oligonucleotides embedded nucleic acid modules are self-assembled with simple photosensitizer aggregates, after which a carrier-free concept is constructed to perform an efficient corporate biological delivery. For another, a light-responsive behavior is integrated by inserting the target identification domain with a photocleavage-linker to avoid the always-active initiation in biological medium, whereby the sensing phase can be manually activated via an external irradiation of a 365 nm ultraviolet light, ensuring a precise diagnostic information to implement the subsequent therapy phase. By conducting a catalyzed hairpin assembly propelled amplification detection to a potential breast cancer associated microRNA biomarker (miRNA-21), this sensing system is discovered to possess satisfactory sensitivity and specificity. Moreover, the further combination of such sensing initiation light and a near-infrared light can offer a peculiar cascaded light-responsive switching to not only realize a high-performance bioimaging in living cells and bodies, but also a high-efficiency photodynamic and gene incorpo-rated dual-mode therapy to solid tumors, giving a robust sensing-to-therapy DNA amplifier.

Automated summary

Despite the powerful capability of DNA amplifiers in sensing low-abundance analytes in living biosystems, their usage of complicated carriers and uncontrollable sensing phase pose difficulties in therapeutic application. In this study, we have developed a carrier-free concept by self-assembling antisense oligonucleotides embedded nucleic acid modules with simple photosensitizer aggregates, enabling efficient biological delivery. Furthermore, we have integrated a light-responsive behavior by inserting a target identification domain with a photocleavage-linker, allowing manual activation of the sensing phase via external irradiation. This robust sensing-to-therapy DNA amplifier exhibits satisfactory sensitivity and specificity for detecting potential breast cancer biomarkers.