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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
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CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance

Xiajing Gu1, Yuanyuan Qiu1, Miao Lin1

  • 1Department of Nuclear Medicine, Clinical and Fundamental Research Center, Institute of Molecular Medicine, Ren Ji Hospital, and Department of Pharmacology and Chemical Biology, Translational Medicine Collaborative Innovation Center , Shanghai Jiao Tong University School of Medicine , Shanghai 200025 , China.

Nano Letters
|April 13, 2019
PubMed

Insights

Copper sulfide nanoparticles (CuS NPs) offer a novel approach to combat gefitinib resistance in non-small cell lung cancer. These nanoparticles, when activated by near-infrared laser, specifically target and inhibit bypass signaling in resistant tumor cells, enhancing gefitinib efficacy.

Area of Science:

  • Nanomedicine
  • Cancer Therapy
  • Molecular Biology

Background:

  • Acquired resistance to gefitinib, a targeted therapy for non-small cell lung cancer (NSCLC), is often driven by bypass signaling pathways.
  • Current strategies to overcome this resistance, such as small-molecule inhibitors and monoclonal antibodies, face challenges due to complex production and off-target toxicity.

Purpose of the Study:

  • To investigate the potential of copper sulfide nanoparticles (CuS NPs) as a photodynamic nanoswitch to overcome gefitinib resistance.
  • To specifically abrogate bypass signaling in gefitinib-resistant tumor cells without affecting normal cells.

Main Methods:

  • CuS nanoparticles were utilized as a photodynamic agent activated by near-infrared laser irradiation.
  • The study focused on tumors with insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistance.
  • Reactive oxygen species (ROS) generation was induced in tumor cells upon laser irradiation to block signaling cascades.

Main Results:

  • CuS NPs, upon laser irradiation, generated localized reactive oxygen species (ROS) in resistant tumor cells.
  • This photodynamic action effectively blocked the IGF1R bypass signaling pathway and its downstream AKT/ERK/NF-κB cascades.
  • Laser-activated CuS NPs sensitized resistant tumors to gefitinib treatment and significantly improved survival in mice without apparent toxicity.

Conclusions:

  • Laser-activated CuS NPs represent a simple, safe, and specific nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in NSCLC.
  • This approach offers a controllable method to target resistant tumors and holds promise for treating other resistant cancers.
Keywords:
CuS nanoparticlesGefitinibdrug resistancenon-small cell lung cancerreactive oxygen species

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