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Electrotaxis Studies of Lung Cancer Cells using a Multichannel Dual-electric-field Microfluidic Chip

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An electrically activable nanochip to intensify gas-ionic-immunotherapy.

Gang Wang¹, Jingrui Li¹, Shumin Sun¹

¹Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.

Science Bulletin

|December 12, 2024

Summary

An electrically activable zinc sulfide (ZnS) nanochip delivers hydrogen sulfide (H2S) and zinc ions (Zn2+) for enhanced gas-ionic-immunotherapy (GIIT), effectively eliminating tumors and boosting immune response.

Keywords:

Cell pyroptosis Electrically controlled delivery H(2)S gas therapy Ionic interference therapy cGAS-STING pathway

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Area of Science:

Biomedical Engineering
Nanotechnology
Cancer Immunotherapy

Background:

Excess intracellular hydrogen sulfide (H2S) causes mitochondrial toxicity.
Zinc ion (Zn2+) overload induces pyroptosis and enhances tumor immunogenicity.
Precise co-delivery of H2S and Zn2+ for cancer therapy remains challenging.

Purpose of the Study:

To develop an electrically activable ZnS nanochip for controlled co-release of H2S and Zn2+.
To investigate the efficacy of this nanochip in gas-ionic-immunotherapy (GIIT).
To explore the underlying mechanisms of tumor elimination and immune response activation.

Main Methods:

Fabrication of an electrically activable ZnS nanochip.
Voltage-controlled degradation of ZnS nanoparticles (NPs) for H2S and Zn2+ release.
In vitro and in vivo studies to evaluate therapeutic efficacy and immune response.

Main Results:

ZnS nanochip-mediated therapy induced mitochondrial dysfunction and oxidative stress in tumor cells.
Activation of the cGAS-STING pathway and pyroptosis enhanced tumor immunogenicity.
Electrically stimulated ZnS nanochip therapy effectively eliminated tumors and mobilized cytotoxic T lymphocytes.
Combination with αCTLA-4 further promoted adaptive immunity and inhibited tumor recurrence.

Conclusions:

The electrically activable ZnS nanochip enables effective GIIT by controlled co-delivery of H2S and Zn2+.
This approach triggers mitochondrial toxicity, pyroptosis, and enhances anti-tumor immunity.
The developed nanochip holds promise for electric stimulation-based cancer therapy and immunotherapy.