Development of multifunctional stimuli-responsive nanomedicine is appealing for effective cancer treatment. Herein, we utilize the biocompatible CaCO₃ nanoparticles as the template to guide the formation of pH-dissociable hollow coordination nanostructures, in which meso-tetra-(4-carboxyphenyl)porphine (TCPP), a sonosensitizer, acts as the organic bridging molecule and ferric ion serves as the metallic center. L-buthionine sulfoximine (BSO), an inhibitor for glutathione (GSH) biosynthesis, can be simultaneously loaded during the preparation of TCPP-Fe@CaCO₃, obtaining BSO-TCPP-Fe@CaCO₃ with pH-responsive dissociation to endow fast release of Ca²⁺ and BSO under an acidic tumor microenvironment. Such BSO-TCPP-Fe@CaCO₃ confers synergistic oxidative stress amplification via intracellular Ca²⁺-overloading-induced mitochondria damage, BSO-mediated GSH depletion, and TCPP-mediated sonodynamic therapy (SDT), leading to remarkable cell death. Consequently, tumors on the mice treated with BSO-TCPP-Fe@CaCO₃ administration and subsequent ultrasound exposure are effectively suppressed. Our work thus highlights a facile strategy to prepare pH-dissociable nanomedicine for effective SDT treatment of tumors via triple amplification of tumor oxidative stress.

多功能刺激响应性纳米医学的发展吸引了有效的癌症治疗。在本文中，我们利用生物相容性CaCO ₃纳米颗粒作为模板来指导pH分解的中空配位纳米结构的形成，其中声敏剂Meso-tetra-（4-羧苯基）卟啉（TCPP）作为有机桥连分子，并且铁离子充当金属中心。可以在制备TCPP-Fe @ CaCO _3的同时装载谷胱甘肽（GSH）生物合成抑制剂L-丁硫氨酸亚砜（BSO），获得具有pH响应解离作用的BSO-TCPP-Fe @ CaCO ₃，从而赋予其快速释放的能力。酸性肿瘤微环境下Ca ²⁺和BSO的变化 此类BSO-TCPP-Fe @ CaCO ₃通过细胞内Ca ²⁺超负荷诱导的线粒体损伤，BSO介导的GSH耗竭和TCPP介导的声动力学疗法（SDT）赋予协同氧化应激放大作用，从而导致明显的细胞死亡。因此，有效抑制了用BSO-TCPP-Fe @ CaCO ₃处理的小鼠的肿瘤以及随后的超声暴露。因此，我们的工作突出了一种简便的策略，即通过三倍放大肿瘤氧化应激来制备可pH分离的纳米药物，以有效地SDT治疗肿瘤。