Bundling gold nanorods with RCA-produced DNA tape into an intelligently reconfigurable nanocluster bomb for multimodal precision cancer therapy

Via proposing an innovative assembly technique, we bundle cell-targeting aptamer-modified gold nanorods (AuNRs) with RCA product (RCA-p) tape into a reconfigurable nanocluster (ARGN) bomb for multimodal precision cancer therapy. Because each ARGN has 10 individual AuNRs, the short time of laser irradiation can make the temperature increase to 75 °C much higher than the lethal temperature of tumor cells, enabling the efficient photothermal therapy (PTT). Moreover, both siRNA-Plk1 (2820 per ARGN) and chemotherapeutic agents (15860 per ARGN) can be loaded into two specifically-designed containers in the internal cavity. Because the glomeroplasmatic structure enhances the resistance to enzymatic degradation, ARGN bomb can protect siRNAs from the digestion and avoid Dox leakage during <i>in vivo</i> circulation. Moreover, the spontaneous structural reorganization allows aptamers in the interior cavity move outward to the exterior surface, which magically offers the compensation of degraded aptamers and impair persistent <i>in vivo</i> cell targeting ability. The external stimuli (laser irradiation) promotes the release of chemotherapeutic agents and initiates the PTT/chemotherapy outcome, while endogenous stimuli (intracellular biomarkers) causes almost 100 % release of siRNA-Plk1 species and induces RNA interference therapy, completely inhibiting tumor growth without detectable off-target toxicity.