由于肿瘤的高死亡率和发病率以及肿瘤微环境(TME)的特异性，使用单一治疗方法很难实现对肿瘤的完全治愈。本研究制备了碳酸钙修饰的钯氢化物纳米颗粒(PdH@CaCO3)，并利用其进行肿瘤的化学动力治疗(CDT)、光热治疗(PTT)和钙超负荷治疗的联合治疗。PdH@CaCO3进入肿瘤细胞后，由于碳酸钙包覆层的pH活性，它会释放出钙离子(Ca2+)和PdH。钙离子(Ca2+)会降低线粒体膜电位，导致细胞不可逆性损伤。与此同时，PdH通过Fenton反应与TME中过量的双氧水(H2O2)发生反应，产生羟基自由基(·OH)。此外，PdH是一种优秀的光热剂，在激光照射下可以杀死肿瘤细胞，产生显著的抗肿瘤效果。体外和体内研究表明，PdH@CaCO3能够结合CDT/PTT和钙超负荷治疗，具有很大的临床治疗潜力。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Due to the high mortality and incidence rates associated with tumors and the specificity of the tumor microenvironment (TME), it is difficult to achieve a complete cure for tumors using a single therapy. In this study, calcium carbonate-modified palladium hydride nanoparticles (PdH@CaCO3) were prepared and utilized for the combined treatment of tumors through chemodynamic therapy (CDT)/photothermal therapy (PTT) and calcium overload therapy. After entering tumor cells, PdH@CaCO3 releases calcium ions (Ca2+) and PdH once it reaches the TME due to the pH reactivity of the calcium carbonate coating. The mitochondrial membrane potential is lowered by the Ca2+, leading to irreversible cell damage. Meanwhile, PdH reacts with excessive hydrogen peroxide (H2O2) in the TME via the Fenton reaction, generating hydroxyl radicals (·OH). Moreover, PdH is an excellent photothermal agent that can kill tumor cells under laser irradiation, leading to significant anti-tumor effects. In vitro and in vivo studies have demonstrated that PdH@CaCO3 could combine CDT/PTT and calcium overload therapy, exhibiting great clinical potential in the treatment of tumors.Copyright © 2023 Elsevier B.V. All rights reserved.