雷公藤红醇 (CEL) 是一种从雷公藤根中分离出来的活性化合物，具有广泛的抗癌活性。然而，其稳定性差、治疗窗口窄以及众多的不良反应限制了其在体内的应用。在这项研究中，设计、合成了三磷酸腺苷（ATP）可激活的CEL-Fe（III）螯合物，然后用活性氧（ROS）响应性聚合物封装以获得CEL-Fe纳米粒子（CEL-Fe NPs）。在正常组织中，CEL-Fe NPs 保持结构稳定性并表现出降低的全身毒性，而在肿瘤部位，富含 ATP-ROS 的肿瘤微环境中，ROS 触发药物释放，并通过 ATP 的竞争性结合恢复抗肿瘤效力。这种智能 CEL 输送系统提高了 CEL 用于癌症治疗的生物安全性和生物利用度。这种 CEL-金属螯合物策略不仅减轻了与 CEL 相关的挑战，而且还为 CEL 衍生物的生成开辟了途径，从而扩大了 CEL 在临床环境中的治疗潜力。

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.