State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Biosens Bioelectron. 2022 Dec 15;218:114763. doi: 10.1016/j.bios.2022.114763. Epub 2022 Oct 5.
Mitochondrion has emerged as a promising drug target for photodynamic therapy (PDT), due to its significant role in supporting life activities and being reactive oxygen species (ROS)-sensitive. Herein, we establish a new strategy that in-situ bio-synthesized Au NCs combine with mitochondria-targeted aptamer-Pyro conjugates (ApPCs) for specific tumor imaging and PDT. The prepared ApPCs can serve as template for the in-situ bio-synthesis of Au NCs, thereby facilitating the generation of Au NCs-ApPCs assemblies in unique tumor microenvironment. Compared with highly negatively charged ApPCs, bio-synthesized nanoscale Au NCs-ApPCs assemblies are conducive to cell uptake, which consequently benefits the delivery of ApPCs. After dissociated from Au NCs-ApPCs, internalized ApPCs can selectively accumulate in mitochondria and generate excess ROS to disrupt the mitochondrial membrane upon irradiation, thus inducing efficient cell killing. In vitro assays demonstrated that the fluorescent Au NCs-ApPCs assemblies could be specifically produced in cancerous cells, indicating the specific tumor imaging ability, while intracellular ApPCs co-localized well with mitochondria. CCK-8 results revealed over 80% cell death after PDT. In vivo study showed that fluorescent Au NCs-ApPCs assemblies were exclusively generated in tumor and achieved long-term retention; tumor growth was significantly inhibited after 15-day PDT treatment. All these evidences suggest that in-situ bio-synthesized Au NCs-ApPCs assembly is a potent mitochondria-targeted nanoprobe to boost the PDT efficacy of cancers.
线粒体已成为光动力疗法 (PDT) 的一个有前途的药物靶点，因为它在支持生命活动和对活性氧物种 (ROS) 敏感方面具有重要作用。在此，我们建立了一种新策略，即原位生物合成的 Au NCs 与线粒体靶向适体-吡咯缀合物 (ApPCs) 结合，用于特异性肿瘤成像和 PDT。制备的 ApPCs 可以作为原位生物合成 Au NCs 的模板，从而促进 Au NCs-ApPCs 组装体在独特的肿瘤微环境中生成。与带高度负电荷的 ApPCs 相比，生物合成的纳米级 Au NCs-ApPCs 组装体有利于细胞摄取，从而有利于 ApPCs 的传递。从 Au NCs-ApPCs 中解离后，内化的 ApPCs 可以选择性地积聚在线粒体中，并在照射时产生过量的 ROS 破坏线粒体膜，从而诱导有效的细胞杀伤。体外实验表明，荧光 Au NCs-ApPCs 组装体可以在癌细胞中特异性产生，表明具有特异性肿瘤成像能力，而细胞内 ApPCs 与线粒体很好地共定位。CCK-8 结果显示 PDT 后超过 80%的细胞死亡。体内研究表明，荧光 Au NCs-ApPCs 组装体仅在肿瘤中产生并实现长期保留；经过 15 天的 PDT 治疗后，肿瘤生长明显受到抑制。所有这些证据表明，原位生物合成的 Au NCs-ApPCs 组装体是一种有效的线粒体靶向纳米探针，可以增强癌症的 PDT 疗效。
