金属过氧化物纳米材料作为高效的过氧化氢（H2O2）自供给剂，在抗肿瘤治疗方面引起了研究人员的关注。然而，仅仅依靠金属过氧化物提供H2O2无疑不足以达到最佳的抗肿瘤效果。在此，我们通过将钯纳米颗粒（Pd NPs）装饰到过氧化镁（MgO2）纳米花的表面来构建新型透明质酸（HA）修饰的纳米复合材料（MgO2/Pd@HA NCs），作为肿瘤微环境的高效纳米平台(TME) 响应性诱导肿瘤细胞铁死亡和肿瘤光热疗法 (PTT)。依靠HA与CD44的特异性识别，MgO2/Pd@HA NC可以很好地内吞到表达CD44的肿瘤细胞中，然后，纳米复合材料可以在弱酸和透明质酸酶过表达的TME中快速分解，并释放出大量的H2O2。同时，Pd NPs由于其过氧化物酶和谷胱甘肽氧化酶模拟酶的活性，催化自身提供的H2O2产生丰富的羟自由基（·OH）并催化谷胱甘肽（GSH）生成谷胱甘肽二硫化物，而丰富的·OH也可以消耗肿瘤细胞中的GSH并干扰铁死亡的防御途径，导致脂质过氧化的积累，导致铁死亡的发生。此外，Pd NPs在近红外II中优异的光热转换性能也可用于PTT，与纳米复合材料诱导的铁死亡协同作用以抑制肿瘤。因此，成功制备的TME响应性MgO2/Pd@HA NCs表现出显着的抗肿瘤作用，且没有明显的生物毒性，有助于彻底探索纳米复合材料作为一种新型且有前途的肿瘤治疗方法。

Metal peroxide nanomaterials as efficient hydrogen peroxide (H2O2) self-supplying agents have attracted the attention of researchers for antitumor treatment. However, relying solely on metal peroxides to provide H2O2 is undoubtedly insufficient to achieve optimal antitumor effects. Herein, we construct novel hyaluronic acid (HA)-modified nanocomposites (MgO2/Pd@HA NCs) formed by decorating palladium nanoparticles (Pd NPs) onto the surfaces of a magnesium peroxide (MgO2) nanoflower as a highly effective nanoplatform for the tumor microenvironment (TME)-responsive induction of ferroptosis in tumor cells and tumor photothermal therapy (PTT). MgO2/Pd@HA NC could be well endocytosed into tumor cells with CD44 expression depending on the specific recognition of HA with CD44, and then, the nanocomposites can be rapidly decomposed in mild acid and hyaluronidase overexpressed TME, and plenty of H2O2 was released. Simultaneously, Pd NPs catalyze self-supplied H2O2 to generate abundant hydroxyl radicals (•OH) and catalyze glutathione (GSH) into glutathione disulfide owing to its peroxidase and glutathione oxidase mimic enzyme activities, while the abundant •OH could also consume GSH in tumor cells and disturb the defense pathways of ferroptosis leading to the accumulation of lipid peroxidation and resulting in the occurrence of ferroptosis. Additionally, the superior photothermal conversion performance of Pd NPs in near-infrared II could also be used for PTT, synergistically cooperating with nanocomposite-induced ferroptosis for tumor inhibition. Consequently, the successfully prepared TME-responsive MgO2/Pd@HA NCs exhibited marked antitumor effect without obvious biotoxicity, contributing to thoroughly explore the nanocomposites as a novel and promising treatment for tumor therapy.