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Multienzyme-Mimicking LaCoO3 Nanotrigger for Programming Cancer-Cell Pyroptosis
Ke Xu1, Meiqi Chang2, Zeyu Wang3
1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, P. R. China.
Advanced Materials (Deerfield Beach, Fla.)
|May 25, 2023
Summary
This study introduces LaCoO3 nanocrystals that induce pyroptosis, a cell death pathway effective against lung cancer. These nanoenzymes generate reactive oxygen species and release lanthanum ions, enhancing cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Pyroptosis is a programmed cell death mechanism offering an alternative to apoptosis-resistant cancers.
- Lung cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
Purpose of the Study:
- To design and engineer LaCoO3 (LCO) lanthanide-based nanocrystals with multienzyme characteristics.
- To investigate the potential of LCO nanocrystals to induce pyroptosis in lung cancer cells.
- To evaluate the therapeutic efficacy of LCO nanocrystals in combination with ultrasound for lung cancer treatment.
Main Methods:
- LaCoO3 (LCO) nanocrystals were synthesized with multienzyme characteristics.
- LCO nanocrystals were engineered to produce cytotoxic reactive oxygen species (ROS) and release lanthanum ions.
- Ultrasound was employed to enhance the enzymatic activity of LCO nanocrystals.
- In vitro and in vivo studies were conducted to assess the anti-cancer effects.
Main Results:
- LCO nanocrystals exhibited peroxidase- and oxidase-mimicking activities, generating ROS in the tumor microenvironment.
- LCO nanoenzyme reversed hypoxia and enhanced tumor cell sensitivity to ROS.
- Released La3+ ions disrupted the lysosomal membrane, inducing pyroptosis.
- Ultrasound enhanced LCO's enzymatic kinetic rate, amplifying therapeutic effects.
- LCO nanocrystals effectively inhibited lung cancer growth and metastasis in vitro and in vivo.
Conclusions:
- LaCoO3 nanocrystals represent a novel nanoenzyme platform for triggering pyroptosis in lung cancer.
- The combination of LCO nanoenzymes and ultrasound offers a promising strategy for treating lung cancer and metastasis.
- This approach provides a new avenue for cancer therapy by leveraging programmed cell death.
