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CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance
Xiajing Gu1,2; Yuanyuan Qiu1,2; Miao Lin1,2; Kai Cui1,2; Gaoxian Chen1,2; Yingzhi Chen1,2; Chenchen Fan1,2; Yongming Zhang1,2; Lu Xu1,2; Hongzhuan Chen4; Jian-Bo Wan5; Wei Lu3; Zeyu Xiao1,2
Source PublicationNANO LETTERS

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.

KeywordGefitinib Cus Nanoparticles Non-small Cell Lung Cancer Rug Resistance Active Oxygen Species
Indexed BySCIE
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
WOS IDWOS:000467781900074
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Nuclear Medicine, Clinical and Fundamental Research Center, Institute of Molecular Medicine, Ren Ji Hospital
2.Department of Pharmacology and Chemical Biology, Translational Medicine Collaborative Innovation Center, Shanghai Jiao TongUniversity School of Medicine, Shanghai 200025, China
3.Key Laboratory of Smart Drug Delivery, Ministry of Education, and State Key Laboratory of Molecular Engineering of Polymers,School of Pharmacy, Fudan University, Shanghai 201203, China
4.Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai201210, China
5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa,Macao 999078, China
Recommended Citation
GB/T 7714
Xiajing Gu,Yuanyuan Qiu,Miao Lin,et al. CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance[J]. NANO LETTERS,2019,19(5):3344-3352.
APA Xiajing Gu,Yuanyuan Qiu,Miao Lin,Kai Cui,Gaoxian Chen,Yingzhi Chen,Chenchen Fan,Yongming Zhang,Lu Xu,Hongzhuan Chen,Jian-Bo Wan,Wei Lu,&Zeyu Xiao.(2019).CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance.NANO LETTERS,19(5),3344-3352.
MLA Xiajing Gu,et al."CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance".NANO LETTERS 19.5(2019):3344-3352.
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