Integrated Enzyme-Powered DNA-Gold Nanomachine for In Vivo Amplified mRNA Photoacoustic Imaging and Enhanced Tumor Photothermal Therapy

Developing activatable nanotheranostics that can improve diagnostic and therapeutic performances and reduce side effects is highly attractive for precision cancer medicine but remains a daunting challenge. Herein, we develop an integrated enzyme-powered DNA-gold nanomachine (DGNM@CM) for the simultaneous amplification of in vivo mRNA photoacoustic (PA) imaging and tumor-specific photothermal therapy (PTT). The DGNM@CM consists of a gold nanoparticle (AuNP) core, an interlayer of linker DNA and partially complementary DNA duplex, which is bound to aptamer-inhibited DNA polymerase, and an outer layer of the tumor cell membrane (CM). Once specifically internalized by target tumor cells, the tumor-related mRNA target interacts with DGNM@CM, initiating a strand-displacement reaction and releasing an active DNA polymerase. This reaction induces the aggregation of AuNPs, which shift their absorption from the visible to near-infrared region, thereby simultaneously activating PA imaging and PTT. More importantly, the released active DNA polymerase can catalyze the recycling of target mRNA through cyclic strand-displacement polymerization reaction and induce the continuous aggregation of AuNPs, thus realizing significant amplification of both PA imaging signals and PTT efficacy. This DGNM@CM can accurately diagnose tumors in vivo and impressively suppress tumor growth with negligible toxicity. The developed DGNM@CM can be extended for the amplified PA detection of other biomolecules and the activation of therapy by them by changing corresponding DNA sequences, thus possessing broad application prospects in biosensing, bioimaging, and precision disease theranostics.