背景：有效的治疗诊断策略同时带来和使用治疗和诊断功能，作为对抗晚期癌症的尖端工具。研究目标：在这里，我们开发了刺激敏感的治疗诊断剂，由定制的共聚物组成，形成胶束缀合物，携带焦脱镁叶绿酸-a (PyF)，通过 pH 敏感的腙键连接，从而实现肿瘤微环境敏感的光动力疗法 (PDT) 激活效应，荧光或磷光。结果：纳米药物显示出卓越的抗肿瘤 PDT 功效和巨大的肿瘤成像潜力，同时减少了它们在肝脏和脾脏中的积累和潜在的副作用。开发的治疗诊断学在小鼠肉瘤 S180 肿瘤模型中表现出明显的选择性肿瘤高水平积累，48 小时后在健康组织中几乎没有发现 PyF。一旦进入肿瘤，由于 1O2 的产生，λexc = 420 nm 的照射即可达到治疗效果。事实上，治疗后 18 天观察到肿瘤生长几乎完全受到抑制。结论：酸性肿瘤环境中特异性 PyF 释放和激活对于靶向递送和组织分布动力学的明显益处已得到证实。通过 pH 敏感腙键连接的焦脱镁叶绿酸-a (PyF) 结合物显示出其优异的抗肿瘤 PDT 效果，并且在极低剂量的 PyF 下作为先进的治疗诊断学的适用性。© 作者。

Background: Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers. Goals of the Investigation: Here, we develop stimuli-sensitive theranostics consisting of tailored copolymers forming micellar conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds, thus enabling the tumor microenvironment-sensitive activation of the photodynamic therapy (PDT) effect, fluorescence or phosphorescence. Results: The nanomedicines show superior anti-tumor PDT efficacy and huge tumor-imaging potential, while reducing their accumulation, and potentially side effects, in the liver and spleen. The developed theranostics exhibit clear selective tumor accumulation at high levels in the mouse sarcoma S180 tumor model with almost no PyF found in the healthy tissues after 48 h. Once in the tumor, illumination at λexc = 420 nm reaches the therapeutic effect due to the 1O2 generation. Indeed, an almost complete inhibition of tumor growth is observed up to 18 days after the treatment. Conclusion: The clear benefit of the specific PyF release and activation in the acidic tumor environment for the targeted delivery and tissue distribution dynamics was proved. Conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds showed their excellent antitumor PDT effect and its applicability as advanced theranostics at very low dose of PyF.© The author(s).