Abstract
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 in vivo 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 in vivo 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.