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MnCl2 Nanosheet‐Triggered Mn2+ Storm Enhances Tumor Immunotherapy Through PANoptosis Induction and cGAS‐STING Activation
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MnCl2 Nanosheet‐Triggered Mn2+ Storm Enhances Tumor Immunotherapy Through PANoptosis Induction and cGAS‐STING Activation
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Journal Article
MnCl2 Nanosheet‐Triggered Mn2+ Storm Enhances Tumor Immunotherapy Through PANoptosis Induction and cGAS‐STING Activation
2026
Overview
As a vital component of innate immunity, the cGAS‐STING pathway has attracted widespread attention in cancer therapy, among which Mn2+ has emerged as a promising antitumor agent. Combining cGAS‐STING agonists with chemotherapy or cancer vaccines represents an effective strategy to enhance their therapeutic efficacy. In this study, we construct simple manganese chloride nanosheets (MnCl2 NSs) that achieve combined effects resembling those of cGAS‐STING activation, chemotherapy, and in situ vaccination without requiring additional drugs or energy input. The synthesized MnCl2 NSs release high concentrations of Mn2+ into tumor cells, causing a storm of Mn2+. Through the combined effects of osmotic pressure, chemodynamic therapy (CDT), and cGAS‐STING activation, they significantly enhance the cytotoxicity of MnCl2 and induce DNA damage, thereby achieving chemotherapy‐like combined therapeutic effects. Concurrently, tumor cells undergo PANoptosis, leading to the release of damage‐associated molecular patterns (DAMPs) and tumor antigens, which effectively generate an in situ tumor vaccine, ultimately activating both innate (cGAS‐STING) and adaptive (PANoptosis) immune responses. Our study proposes a novel strategy to synergistically enhance immunotherapy by inducing tumor cell PANoptosis while concurrently activating the cGAS‐STING pathway, offering valuable guidance for the design of immunotherapeutic nanomaterials. This study constructs an ultrasound‐assisted liquid‐phase exfoliated MnCl2 nanosheet system for tumor treatment, establishing an immunotherapy strategy combining PANoptosis induction with cGAS‐STING activation. This treatment system does not require the introduction of additional drugs or energy input, enabling multiple combination therapeutic effects with a minimal increase in side effects.
Publisher
Wiley
Subject
