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

Abstract 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.