Nanotherapeutics interfere with cellular redox homeostasis for highly improved photodynamic therapy

Redox homeostasis inside malignant cells is a defense mechanism against the reactive oxygen species (ROS)-induced therapy means, but little importance has been paid to this innate barrier. The present study intends to make cancer cells more sensitive to the ROS-induced therapy by disturbing cellular...

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Bibliographic Details
Published in:Biomaterials 2019-12, Vol.224, p.119500, Article 119500
Main Authors: Cheng, Qian, Yu, Wuyang, Ye, Jingjie, Liu, Miaodeng, Liu, Wenlong, Zhang, Chi, Zhang, Cheng, Feng, Jun, Zhang, Xian-Zheng
Format: Article
Language:English
Subjects:
3T3 Cells
Activating Transcription Factor 4 - metabolism
Animals
Cell Line, Tumor
Dioxolanes - therapeutic use
Drug Liberation
Homeostasis
Humans
Hydrogen-Ion Concentration
Metal-organic framework
Metal-Organic Frameworks - chemistry
Mice
Mice, Inbred BALB C
Nanoparticles - therapeutic use
Oxidation-Reduction
Photochemotherapy
Photodynamic therapy
Reactive oxygen species
Reactive Oxygen Species - metabolism
Redox homeostasis
Thioredoxin reductase
Thioredoxin-Disulfide Reductase - metabolism
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Summary:Redox homeostasis inside malignant cells is a defense mechanism against the reactive oxygen species (ROS)-induced therapy means, but little importance has been paid to this innate barrier. The present study intends to make cancer cells more sensitive to the ROS-induced therapy by disturbing cellular redox homeostasis. To verify this concept, a porous metal-organic framework (MOF) serves not only as the photodynamic therapy (PDT) agent but also as the carrier to transport alkaloid piperlongumine (PL), a thioredoxin reductase (TrxR) inhibitor used to disturb cellular redox homeostasis. The PL-loaded MOF was further coated with cancer cell membranes to gain homologous tumor-targeting capability. Inside tumor cells, the released PL can effectively block the TrxR-mediated ROS elimination pathway. The resultant data show that compared to traditional PDT alone, the combination of PDT and TrxR inhibition causes profound promotions in cellular ROS level by about 1.6 times, in cytotoxicity by about 2 times, and in cellular apoptosis/necrosis rate by about 3 times. Consequently, this strategy based on the interference with cellular redox homeostasis has demonstrated high potency to improve the anticancer PDT performance, adumbrating a new way to boost the power of ROS-induced therapy.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2019.119500