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Electrical stimulation induces anti-tumor immunomodulation via a flexible microneedle-array-integrated interdigital
Yixuan Pan1, Yangxi Zhang2, Xueying Shi1
1Key Laboratory of Smart Biomaterials of Zhejiang Province, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Science Bulletin
|October 20, 2023
Summary
This study introduces a novel flexible microneedle electrode for electrical stimulation (ES) cancer therapy. This drug-free approach effectively targets cancer cells, enhances immune response, and inhibits tumor growth.
Area of Science:
- Biomedical Engineering
- Oncology
- Immunology
Background:
- Immunotherapy revolutionized cancer treatment but faces challenges with tumor penetration and side effects.
- Electrical stimulation (ES) offers a drug-free alternative but requires advanced microfabrication.
- Existing ES devices often lack the complexity for effective cancer therapy.
Purpose of the Study:
- To develop and evaluate a novel optically microprinted flexible interdigital electrode with a microneedle array for cancer treatment.
- To investigate the mechanisms of cancer cell death induced by this new ES device.
- To assess the immunomodulatory effects and systemic anti-tumor efficacy of the FMIE-based ES.
Main Methods:
- Fabrication of a flexible microneedle-array-integrated interdigital electrode (FMIE) using optical 3D microprinting and electroless plating.
- Application of FMIE-mediated alternating electric fields to cancer cells.
- Analysis of cell death mechanisms, including mitochondrial Ca2+ overload and reactive oxygen species (ROS) production.
- Evaluation of damage-associated molecular patterns (DAMPs) release and immune response activation.
- Assessment of systemic anti-tumor effects in preclinical models, including primary tumors, distant tumors, and lung metastasis.
Main Results:
- FMIE-mediated ES induced cancer cell death via mitochondrial Ca2+ overload and increased ROS production.
- This process led to the release of DAMPs, activating immune responses and potentiating immunogenic cell death (ICD).
- FMIE-based ES demonstrated a favorable safety profile and significant systemic anti-tumor effects, inhibiting primary and distant tumor growth and melanoma lung metastasis.
Conclusions:
- The developed FMIE is an effective platform for drug-free cancer therapy using electrical stimulation.
- FMIE-based ES promotes immunogenic cell death and harnesses the immune system for anti-tumor effects.
- This technology presents a promising new avenue for cancer immunomodulation and treatment.
