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The physiological parameters are often dynamically changing during disease progression, such as cancer, infections, and degenerative diseases, rendering them not only attractive biomarkers for disease diagnosis, but also potential tools for self healing. With the deep understanding of cancer, masses of bioresponsive smart systems were designed for precision cancer medications, engaging biological triggers or pathological abnormalities such as pH, redox, enzyme, biomolecules, shear force, hypoxia, etc. In our work, we have chosen the endogenous microRNA as specific triggers and biomarkers for cancer diagnosis and treatment. To address the issue of low copy numbers of microRNA in single cells, we developed programmable nanodevices consisting of gold nanorods and MNAzymes to realize stringent recognition and in situ amplification of intracellular miRNAs for multiplexed detection and controlled drug release. Furthermore, smart nanocarriers were prepared to achieve specific and efficient release of Dox and siRNAs in tumor cells via enzyme-free cascade amplification with endogenous microRNA as trigger and ATP as fuel through toehold-mediated strand displacement. On the other hand, to maximize specific tumor uptake and minimize off-target internalization in in vivo study, the surface of the nanocarriers were engineered by using temperature sensitive polymers. The in vivo results showed that a low dosage of nanocarriers could precisely enter the tumor under the NIR laser guidance, releasing the cargoes and inducing severe cell apoptosis, though they only brought minimum damage to normal organs. The combination of nanomaterials, polymers, and DNA nanomachines provided a promising tool for designing smart nanodevices for precise disease diagnosis and treatment.
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