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Bimetallic peroxide nanoparticles induce PANoptosis by disrupting ion homeostasis for enhanced immunotherapy
Guanghui Hou1, Youdong Chen1, Huali Lei1
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
Abstract:
PANoptosis has recently emerged as a potential approach to improve the immune microenvironment. However, current methods for inducing PANoptosis are limited. Herein, through biological screening, the rational use of the nutrient metal ions Cu2+ and Zn2+ had great potential to induce PANoptosis. Inspired by these findings, we successfully developed hydrazided hyaluronic acid-modified zinc copper oxide (HZCO) nanoparticles as a PANoptosis inducer to potentiate immunotherapy. Bioactive HZCO actively delivered Cu2+ and Zn2+ while disrupting the cellular intrinsic ion metabolism pathway, resulting in double-stranded DNA release and organelle damage in cancer cells. Simultaneously, this process triggered the formation of PANoptosome and the activation of PANoptosis. HZCO-induced PANoptosis inhibited tumor growth and activated potent antitumor immune response, thereby enhancing the effectiveness of anti-programmed cell death 1 therapy. Overall, our work provides an insight into the development of PANoptosis inducers and the design of synergistic immunotherapy strategies.
Insights
Researchers developed novel zinc copper oxide nanoparticles (HZCO) to induce PANoptosis, a cell death pathway. This approach enhances immunotherapy by inhibiting tumor growth and activating anti-tumor immune responses, offering new strategies for cancer treatment.
Area of Science:
- Biomedical Engineering
- Immunology
- Nanotechnology
Background:
- PANoptosis is an emerging cell death pathway with potential for immune microenvironment modulation.
- Existing methods for inducing PANoptosis are limited, necessitating novel approaches.
Purpose of the Study:
- To develop a novel PANoptosis inducer for potentiating cancer immunotherapy.
- To investigate the potential of nutrient metal ions (Cu²⁺ and Zn²⁺) in inducing PANoptosis.
Main Methods:
- Biological screening identified Cu²⁺ and Zn²⁺ as potential PANoptosis inducers.
- Development of hydrazided hyaluronic acid-modified zinc copper oxide (HZCO) nanoparticles.
- Evaluation of HZCO's ability to induce PANoptosis, disrupt ion metabolism, and trigger immune responses in cancer cells.
Main Results:
- HZCO nanoparticles effectively delivered Cu²⁺ and Zn²⁺, disrupting cellular ion metabolism and causing DNA release and organelle damage.
- HZCO induced PANoptosis via PANoptosome formation and activation.
- HZCO-mediated PANoptosis inhibited tumor growth and enhanced antitumor immunity, improving anti-programmed cell death 1 therapy efficacy.
Conclusions:
- HZCO nanoparticles serve as an effective PANoptosis inducer for cancer therapy.
- This study offers insights into developing novel PANoptosis inducers and synergistic immunotherapy strategies.
