National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, P. R. China.
National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Chemistry and Biomedicine Innovation Center, School of Physics, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, 210093, P. R. China.
Small. 2023 Nov;19(45):e2302952. doi: 10.1002/smll.202302952. Epub 2023 Jul 11.
Zinc has been proven to interweave with many critical cell death pathways, and not only exhibits potent anticancer activity solely, but sensitizes cancer cells to anticancer treatment, making zinc supplementation ideal for boosting odds against malignancy. Herein, a smart nanorobot (termed as Zinger) is developed, composed of iRGD-functionalized liposome encapsulating black phosphorus nanosheet (BPNs) doped zeolite imidazole framework-8 (BPN@ZIF-8), for advancing zinc-promoted photodynamic therapy (PDT). Zinger exhibits photo-triggered sequential mitochondria-targeting ability, and can induce zinc overload-mediated mitochondrial stress, which consequently sensitized tumor to PDT through synergistically modulating reactive oxygen species (ROS) production and p53 pathway. It is identified that Zinger selectively triggered intracellular zinc overload and photodynamic effect in cancer cells, which together enhanced PDT treatment outcomes. Importantly, Zinger shows high efficacy in overcoming various treatment barriers, allowing for effectively killing cancer cells in the complex circumstances. Particularly, Zinger exhibits good tumor accumulation, penetration, and even cell uptake, and can respond to light stimulation to eliminate tumors while avoiding normal tissues, thereby prolonging survival of tumor-bearing mice. Therefore, the study provides a novel insight in the development of novel zinc-associated therapy for advancing cancer treatment approaches.
锌已被证明可与许多关键的细胞死亡途径交织在一起，不仅单独表现出强大的抗癌活性，还能使癌细胞对癌症治疗敏感，使锌补充成为提高抗癌几率的理想选择。在此，开发了一种智能纳米机器人（称为 Zinger），它由 iRGD 功能化脂质体包裹掺杂沸石咪唑酯骨架-8（BPN@ZIF-8）的黑磷纳米片（BPNs）组成，用于推进锌促进的光动力疗法（PDT）。Zinger 具有光触发的顺序靶向线粒体能力，并能诱导锌过载介导的线粒体应激，从而通过协同调节活性氧（ROS）产生和 p53 途径使肿瘤对 PDT 敏感。研究表明，Zinger 选择性地在癌细胞中引发细胞内锌过载和光动力效应，共同增强了 PDT 治疗效果。重要的是，Zinger 能够克服各种治疗障碍，在复杂情况下有效地杀死癌细胞。特别是，Zinger 表现出良好的肿瘤积累、渗透，甚至细胞摄取能力，并能响应光刺激消除肿瘤，同时避免正常组织，从而延长荷瘤小鼠的存活时间。因此，该研究为开发新型锌相关治疗方法以推进癌症治疗方法提供了新的思路。
