肿瘤微环境
纳米材料基催化剂
光热治疗
细胞内
巨噬细胞
材料科学
癌症研究
化学
生物物理学
纳米技术
体外
纳米颗粒
生物
生物化学
肿瘤细胞
作者
Wenbao Zuo,Weibin Chen,Jinxue Liu,Shuying Huang,Luping Chen,Qingna Liu,Nian Liu,Quanyi Jin,Yang Li,Peiyuan Wang,Xuan Zhu
标识
DOI:10.1021/acsami.1c22432
摘要
Fe-based nanomaterials with Fenton reaction activity are promising for tumor-specific chemodynamic therapy (CDT). However, most of the nanomaterials suffer from low catalytic efficiency due to its insufficient active site exposure and the relatively high tumor intracellular pH, which greatly impede its clinical application. Herein, macrophage membrane-camouflaged carbonic anhydrase IX inhibitor (CAI)-loaded hollow mesoporous ferric oxide (HMFe) nanocatalysts are designed to remodel the tumor microenvironment with decreased intracellular pH for self-amplified CDT. The HMFe not only serves as a Fenton agent with high active-atom exposure to enhance CDT but also provides hollow cavity for CAI loading. Meanwhile, the macrophage membrane-camouflaging endows the nanocatalysts with immune evading capability and improves tumoritropic accumulation by recognizing tumor endothelium and cancer cells through α4/VCAM-1 interaction. Once internalized by tumor cells, the CAI could be specifically released, which can not only inhibit CA IX to induce intracellular H+ accumulation for accelerating the Fenton reaction but also could prevent tumor metastasis because of the insufficient H+ formation outside cells for tumor extracellular matrix degradation. In addition, the HMFe can be employed to highly efficient magnetic resonance imaging to real-time monitor the agents' bio-distribution and treatment progress. Both in vitro and in vivo results well demonstrated that the nanocatalysts could realize self-amplified CDT and breast cancer metastasis inhibition via tumor microenvironment remodeling, which also provides a promising paradigm for improving CDT and antimetastatic treatment.
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