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Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-05-18 , DOI: 10.1021/acsami.3c02929
Liefeng Hu 1, 2 , Chuxiao Xiong 1, 2 , Jun-Jie Zou 1, 2 , Junrong Chen 1, 2 , Hengyu Lin 3 , Scott J Dalgarno 4 , Hong-Cai Zhou 3 , Jian Tian 1, 2
Affiliation  

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel “all-in-one” chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal–organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.

中文翻译:

工程化 MOF-酶纳米复合材料用于具有自发光和自供氧的肿瘤微环境激活光动力疗法

光动力疗法 (PDT) 是一种很有前途的癌症治疗策略。然而,其效率受到三个关键参数的阻碍,即外部光的有限穿透深度、肿瘤缺氧和光敏剂的自聚集。在此,我们通过将供氧蛋白(血红蛋白,Hb)和发光供体(鲁米诺,Lum)整合到分层设计的介孔卟啉金属有机骨架中,构建了一种新型的“一体式”化学发光-PDT 纳米系统( MOF)纳米粒子。从机理上讲,Lum 的原位化学发光是由高浓度的 H 2 O 2激活的在 4T1 癌细胞中,进一步被 Hb 催化,然后通过化学发光共振能量转移被 MOF 纳米粒子中的卟啉配体吸收。兴奋的卟啉然后使 Hb 提供的氧气敏感,产生足够的活性氧来杀死癌细胞。基于 MOF 的纳米复合材料在体外和体内均表现出优异的抗癌活性,在没有外部光照射的情况下静脉注射后最终具有 68.1% 的肿瘤抑制率。这种自发光、自供氧的纳米系统将 PDT 的所有基本成分集成到一个简单的纳米平台中,展示了选择性光疗深部癌症的巨大潜力。
更新日期:2023-05-18
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