A Near‐Infrared Photo‐Switched MicroRNA Amplifier for Precise Photodynamic Therapy of Early‐Stage Cancers

Stimuli-responsive photodynamic therapy (PDT) is a hot topic in precise medicine, but the low abundance of responsive trigger molecules in early-stage disease limits application. Here we designed an amplifier with multiple upconversion luminances to achieve a near-infrared photo-switched cascade reaction triggered by specific microRNA and precise PDT of early-stage cancers. This amplifier was composed of photo-caged DNA nanocombs and an upconversion nanoparticle (UCNP) sensitized with IRDye 800CW. The nanocomb was prepared by assembling a photozipper-protected hairpin and two kinds of hybridizable hairpin probes on a DNA skeleton. Upon 808-nm light irradiation, the produced UV light cleaved off the photozipper to induce microRNA-responsive cascade hybridization reaction, activating the photosensitizers linked to different hairpins to generate reactive oxygen species (ROS) under the simultaneously emitted blue light for efficient PDT.