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 photoswitched 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 photozipperprotected 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.

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…By confining free nucleic acid probes in the space along the 1D compact DNA nanostructure, the nanowire can hold different probes, thus transforming the regular "intermolecular" reaction into an "intramolecular" mode. 18,19 It means the probes can maintain a high local concentration, which greatly improves the reaction efficiency and shortens the reaction time. 20 Wang et al 21 reported a DNA nanowire-based localized catalytic hairpin assembly (LCHA) reaction for miRNA imaging in living cells (Fig.…”

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

“…In an alternative approach, molecular beacon probes were successfully developed for selectively targeting oligonucleotides, displaying a turn-on 1 O 2 -production in the presence of the complementary target, taking advantage of the quenching effect when the probes are not hybridized to their natural target [ 302 , 303 , 304 , 305 , 306 , 307 ] ( Figure 19 B), due to the presence of a quencher. The use of these molecular beacons has several advantages over the use of regular probes, since the 1 O 2 generation can be selectively induced, only in the presence of a complementary target, able to open the hairpin structure and separate the PS from its quencher, thus lowering side effects related to an excessive ROS generation.…”

DNA Assembly‐Based Stimuli‐Responsive Systems

“…The precise PDT of early‐stage cancers can be achieved through the generation of ROS by the activation of photosensitizers. [ 377 ] Tan's group linked the photosensitizer molecule chlorin e6 (Ce6) to the aptamer switch probe (ASP), which was modified on the surface of gold nanorods (AuNRs) for PTT, achieving synergistic therapeutic effect of cancer (Figure 11d). [ 373 ] They also developed a Ce6‐DNAzyme‐MnO 2 nanosystem for synergistic therapy with gene silence and PDT, in which MnO 2 nanosheets were used as protective and activator of DNAzymes for gene silencing, and photosensitizer Ce6 for PDT.…”