MicroRNA-triggered in situ programmed assembly of photosensitizers with controlled dimension and accelerated kinetics for precise cancer therapy

利用microRNA触发原位程序化组装具有可控尺寸和加速动力学的光敏剂,实现精准癌症治疗

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Abstract

The selective in situ synthesis and activation of therapeutic agents within tumor cells are critical for enhancing the targetability and preciseness of cancer therapy. Herein, triggered by specific tumor microRNA biomarkers, programmed hybridization-chain reaction (HCR) assemblies of aggregation-induced emission (AIE) photosensitizers were conducted for the in situ, rapid and controllable synthesis of anticancer agents in cancer cells. Robust fluorescence and photodynamic activities were thus provoked from scratch for precise cancer therapy. By precisely tuning the DNA valency conjugated to the photosensitizer, controllable assembly of one-dimensional linear-, two-dimensional dendritic-, and three-dimensional spherical-type structures were achieved, in which the two-dimensional assembly showed the greatest gains in turn-on fluorescence and reactive oxygen species (ROS) signals. Notably, the photosensitizer conjugation significantly accelerated the HCR kinetics of hairpin DNAs, thereby facilitating the rapid response to microRNA biomarkers within tumor cells and tissues. This microRNA-responsive kinetics-accelerated and dimension-controllable assembly strategy, provides a new avenue for in situ precise cancer theranostics.

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