Smart down/upconversion nanomachines integrated with "AND" logic computation and enzyme-free amplification for NIR-II fluorescence-assisted precise and enhanced photodynamic therapy.

Upconversion nanoparticles enable indirect activation of photodynamic therapy (PDT) using near-infrared (NIR) light, providing an excellent alternative for treating deep tumors. However, conventional NIR light-triggered PDT systems suffered from low spatiotemporal accuracy and restricted therapeutic efficiency in vivo . In this work, DNA logic circuits were functionally modified on down/upconversion nanoparticles (D/UCNPs) to construct smart down/upconversion nanomachines (D/UCNMs) for NIR light-triggered PDT toward target tumors. Upon dual inputs of tumor-associated GSH and TK1 mRNA, DNA logic circuits perform "AND" logic computation and initiate the toehold-mediated strand displacement reaction. Meanwhile, the quenched upconversion fluorescence was recovered and then the approaching photosensitizers were activated, leading to in situ output of singlet oxygen ( 1 O 2 ) for precise and enhanced PDT. Importantly, the biodistribution of the D/UCNMs in vivo could be visualized by second near-infrared (NIR-II) fluorescence imaging via the downconversion luminance of D/UCNPs, which further contributed to performing precise PDT. This work provides new insights into the development of precise and highly efficient PDT systems.