A DNA Logic Circuit Equipped with a Biological Amplifier Loaded into Biomimetic ZIF‐8 Nanoparticles Enables Accurate Identification of Specific Cancers In Vivo

DNA logic circuits (DLC) enable the accurate identification of specific cell types, such as cancer cells, but they face the challenges of weak output signals and a lack of competent platforms that can efficiently deliver DLC components to the target site in the living body. To address these issues, we rationally introduced a cascaded biological amplifier module based on the Primer Exchange Reaction inspired by electronic circuit amplifier devices. As a paradigm, three abnormally expressed Hela cell microRNAs (-30a, -17, and -21) were chosen as "AND" gate inputs. DLC response to these inputs was boosted by the amplifier markedly enhancing the output signal. More importantly, the encapsulation of DLC and amplifier components into ZIF-8 nanoparticles resulted in their efficient delivery to the target site, successfully distinguishing the Hela tumor subtype from other tumors in vivo. Thus, we envision that this strategy has great potential for clinical cancer diagnosis.