An Intelligent DNA Nanoreactor for Easy‐to‐Read In Vivo Tumor Imaging and Precise Therapy

Abstract Nanomaterial‐based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent “always ON” or single‐parameter responsive signal output, substantial off‐target effects, and high cost. Therefore, achieving in vivo easy‐to‐read tumor imaging and precise therapy in a multi‐parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the “AND” Boolean logic algorithm to address these issues. iDNR‐mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers “AND” hydrogen peroxide (H 2 O 2 ). Therefore, intelligent temperature‐based in vivo easy‐to‐read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.