CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance
| Autor: | Xiajing Gu, Yingzhi Chen, Miao Lin, Yuanyuan Qiu, Yongming Zhang, Kai Cui, Zeyu Xiao, Gaoxian Chen, Lu Xu, Wei Lu, Chenchen Fan, Hong-Zhuan Chen, Jian-Bo Wan |
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| Rok vydání: | 2019 |
| Předmět: |
MAPK/ERK pathway
medicine.drug_class Antineoplastic Agents Apoptosis Bioengineering 02 engineering and technology Drug resistance Monoclonal antibody Mice Gefitinib Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Animals Humans General Materials Science Protein kinase B Cell Proliferation Insulin-like growth factor 1 receptor chemistry.chemical_classification Reactive oxygen species Chemistry Mechanical Engineering General Chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics Xenograft Model Antitumor Assays Drug Resistance Neoplasm Mutation Cancer research Nanoparticles Nanomedicine 0210 nano-technology Copper medicine.drug |
| Zdroj: | Nano Letters. 19:3344-3352 |
| ISSN: | 1530-6992 1530-6984 |
| Popis: | Bypass signaling activation plays a crucial role in the acquired resistance of gefitinib, the first targeted drug in the clinic to treat advanced non-small cell lung cancer. Although the inactivation of bypass signaling by small-molecule inhibitors or monoclonal antibodies may overcome gefitinib resistance, their clinical use has been limited by the complex production process and off-target toxicity. Here we show CuS nanoparticles (NPs) behaved as a photodynamic nanoswitch to specifically abrogate overactive bypass signaling in resistant tumor cells without interfering with the same signal pathways in normal cells. In representative insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistant tumors, CuS NPs upon near-infrared laser irradiation locally elevated reactive oxygen species (ROS) level in tumor cells, leading to the blockage of bypass IGF1R and its downstream AKT/ERK/NF-κB signaling cascades. Consequently, laser-irradiated CuS NPs sensitized tumors to gefitinib treatment and prolonged the survival of mice with no obvious toxicity. Laser-irradiated CuS NPs may serve as a simple and safe nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in a specific and controllable manner and provide insights into the treatment of a myriad of other resistant tumors in the field of cancer therapy. |
| Databáze: | OpenAIRE |
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