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.
肿瘤细胞内治疗剂的选择性原位合成与激活对于提升癌症治疗靶向性与精准度至关重要。本研究基于特定肿瘤微RNA生物标志物触发，通过程序化杂交链式反应组装聚集诱导发光光敏剂，在癌细胞内实现了抗癌药物的原位、快速、可控合成。由此从无到有激发了强烈的荧光与光动力活性，为精准癌症治疗提供支撑。通过精确调控与光敏剂偶联的DNA价态，成功实现了一维线性、二维树枝状及三维球状结构的可控组装，其中二维组装体在开启式荧光信号与活性氧信号增益方面表现最为显著。值得注意的是，光敏剂偶联显著加速了发夹DNA的杂交链式反应动力学，从而促进了对肿瘤细胞和组织内微RNA生物标志物的快速响应。这种微RNA响应型动力学加速与维度可控的组装策略，为原位精准癌症诊疗提供了新途径。
肿瘤(癌症)患者之家