摘要： To advance anti-tumor efficiency and lessen adverse effect caused by nanodrug residues in body, a smart nanoagent system is developed and successfully used in intracellular ATP-imaging and in vivo chemo-photothermal synergetic therapy. The nanoagent system is facilely prepared using DNA complex to modify gold nanoparticles (AuNPs). The DNA complex is formed by three oligonucleotides (ATP aptamer, rC-DNA and rG-DNA). CG-rich structure in ternary DNA complex could be exploited for payload of chemotherapeutic medicine doxorubicin (DOX), thus making efficient DOX transport into tumor site possible. In tumor cells, especially in acidic organelles (e.g. endosome and lysosome), DOX could be rapidly released via the dual stimuli of over-expressed ATP and pH. What’s more, the specific recognition of fluorescent-labelled aptamer strand to ATP can achieve the intracellular ATP imaging. pH-controlled reversible folding and unfolding of intermolecular i-motif formed by C-rich strands can lead to intracellular in situ assembly of AuNP aggregates with high photothermal conversion efficiency, and promote relatively facile renal clearance of AuNPs through the disassociation of the aggregates in extracellular environments. Experiments in vivo and vitro present feasibility for synergetic chemo-photothermal therapy. Such an in situ reversible assembly strategy of chemo-photothermal agent also presents a new paradigm for smart and highly efficient disease treatment with reduced side effects.