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An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation
Published on: August 30, 2017
Ultrasound-triggered self-assembled cascade nanozymes for ROS-mediated synergistic chemodynamic therapy.
Ziwei Zhao1, Liangyu Li2, Wenjing Qi1
1School of Medical Science and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611130, China; Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing, 400016, China.
This study introduces an ultrasound-triggered nanozyme (HSA-GOx-CuO) that enhances cancer therapy by boosting reactive oxygen species (ROS) and depleting glutathione (GSH). The nanozyme effectively inhibits tumor growth and promotes immune response.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Chemodynamic therapy (CDT) faces limitations due to low reactive oxygen species (ROS) generation and high glutathione (GSH) levels in tumors.
- Developing novel strategies to overcome these challenges is crucial for effective cancer treatment.
Purpose of the Study:
- To develop an ultrasound-triggered, self-assembled cascade nanozyme (HSA-GOx-CuO) for enhanced chemodynamic therapy.
- To investigate the synergistic effects of glucose depletion, ROS amplification, GSH depletion, and CDT.
Main Methods:
- Fabrication of HSA-GOx-CuO nanozyme and evaluation of its properties.
- In vitro assessment of ROS generation, apoptosis induction, and dendritic cell maturation in 4T1 breast cancer cells under ultrasound (US) stimulation.
- In vivo evaluation of tumor inhibition and accumulation in a tumor model.
Main Results:
- HSA-GOx-CuO demonstrated significant ROS elevation, potent apoptosis induction (85.1% late apoptotic rate), and enhanced dendritic cell maturation (97.9% CD80+CD86+ DCs) in vitro.
- In vivo studies showed efficient tumor accumulation and a 92.6% tumor inhibition rate with suppressed tumor growth.
- The nanozyme effectively integrated starvation therapy and GSH depletion for synergistic CDT.
Conclusions:
- The developed US-activatable cascade nanoplatform offers a novel and safe strategy for precision synergistic chemodynamic therapy.
- This approach overcomes key limitations of traditional CDT, showing significant potential for cancer treatment.

