Malignant proliferation of tumor cells induces abnormal tissue microenvironments, leading to therapeutic resistance and poor therapeutic outcome. In this paper, manganese dioxide (MnO₂) nanoshells are coated on a porphyrinic metal–organic framework of porous coordination network (PCN)‐224 for doxorubicin (DOX) loading and hyaluronic acid (HA) modification to obtain an intelligent nanoplatform of PCN@MnO₂@DOX@HA (PMDH). Benefiting from the HA functionalization, PMDH prefers to accumulate in tumor sites and enhance the cellular uptake by CD44‐overexpressed tumor cells. Subsequently, the internalized PMDH could catalyze the abundant H₂O₂ in cells into O₂ to relieve tumor hypoxia. Further, the MnO₂ nanoshells of PMDH could be degraded into Mn²⁺ for magnetic resonance imaging with glutathione reduction and the release of DOX. By integrating the O₂ self‐sufficiency with glutathione reduction abilities, PMDH possesses highly potent chemo/photodynamic combination therapeutic effects against hypoxic tumors. Significantly, PMDH exhibits a good biocompatibility with a low cardiotoxicity and negligible systemic side effects, which provides a new insight in developing tumor microenvironment adaptable nanoplatforms for synergistic tumor theranostics.

中文翻译：

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肿瘤微环境适应性纳米平台，用于氧气自足的化学/光动力联合疗法

肿瘤细胞的恶性增殖诱导异常的组织微环境，导致治疗抗性和不良的治疗结果。在本文中，将二氧化锰（MnO ₂）纳米壳涂在多孔配位网络（PCN）-224的卟啉金属-有机框架上，以进行阿霉素（DOX）负载和透明质酸（HA）修饰，以获得智能的PCN纳米平台MnO ₂ @ DOX @ HA（PMDH）。受益于HA功能化，PMDH倾向于在肿瘤部位积累并增强CD44过表达的肿瘤细胞对细胞的摄取。随后，内在的PMDH可以将细胞中大量的H ₂ O ₂催化转化为O _2，从而减轻肿瘤的缺氧。此外，MnO ₂PMDH的纳米壳可降解为Mn ²⁺，以进行谷胱甘肽还原和DOX释放的磁共振成像。通过将O ₂自给与谷胱甘肽还原能力相结合，PMDH对缺氧肿瘤具有高度有效的化学/光动力联合治疗作用。重要的是，PMDH表现出良好的生物相容性，具有低的心脏毒性和可忽略的全身性副作用，这为开发具有肿瘤微环境适应性的纳米平台用于协同肿瘤治疗学提供了新的见识。