Photodynamic therapy (PDT) and chemotherapy has been applied as a prospective approach in tumor therapeutics. However, suffering from the inherent hypoxia status in tumor microenvironment (TME), the anticancer efficiency is enormously restricted, especially PDT. Herein, we develop a unique liposomal encapsulated catalase (CAT), lyso-targeted NIR photosensitizer (MBDP) and doxorubicin (Dox), forming FA-L@MD@CAT, to increase tumor oxygenation by catalyzing intratumoral high-expressed H2O2 for enhancing the combination of chemo-PDT. Moreover, the enhanced tumoral oxygenation not only facilitates singlet oxygen (1O2) production but also reverses immunosuppressive TME by modulating immune cytokines to favor antitumor immunities, which significantly induce tumor death. Notably, this system also realizes specific tumor recognition to folate receptor upregulated tumors and improves intratumoral accumulation. This work provides an effective strategy to promote tumor therapeutic index, which may possess a promising future in clinical application.

中文翻译：

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用于逆转免疫抑制性肿瘤微环境和增强癌症化学光动力疗法的基于过氧化氢酶的脂质体。

光动力疗法（PDT）和化学疗法已被用作肿瘤治​​疗的前瞻性方法。然而，由于肿瘤微环境（TME）固有的缺氧状态，其抗癌效果受到极大限制，尤其是PDT。在此，我们开发了一种独特的脂质体包裹的过氧化氢酶 (CAT)、溶血靶向 NIR 光敏剂 (MBDP) 和多柔比星 (Dox)，形成 FA-L@MD@CAT，通过催化肿瘤内高表达的 H2O2 来增加肿瘤氧合以增强化学-PDT的组合。此外，增强的肿瘤氧合不仅促进单线态氧 (1O2) 的产生，而且通过调节免疫细胞因子来促进抗肿瘤免疫，从而逆转免疫抑制性 TME，从而显着诱导肿瘤死亡。尤其，该系统还实现了对叶酸受体上调肿瘤的特异性肿瘤识别，并改善肿瘤内积聚。这项工作为提高肿瘤治疗指数提供了一种有效的策略，在临床应用中具有广阔的前景。