Synchronously Delivering Melittin and Evoking Ferroptosis via Tumor Microenvironment‐Triggered Self‐Destructive Metal–Organic Frameworks to Boost Cancer Immunotherapy

• DOI: 10.1002/adhm.202500003
• Publication Date: 2025-03-11T13:49:01Z
• Authors: Dongsheng Zhang; Tingting Wang; Xun Zhang; Yuting Xu; Jiang Ming; Xiaoxiao Wang; Zhenfeng Liu; Jingchao Li; Xinhui Su
• Keywords: Melittin

Abstract The primary goal of treating malignant tumors is to efficiently eliminate the tumor and prevent metastasis recurrence. Unfortunately, immunosuppressive microenvironment (TME) a significant obstacle effective oncotherapy. Herein, therapeutic strategy based on melittin (MLT) encapsulated in hyaluronic acid‐modified metal–organic frameworks (MOFs) pioneered, focusing safe delivery TME‐responsive release MLT reshaping TME simultaneously activating immune system eradicate cancerous cells. Iron‐based MOFs respond glutathione pH, degrade within moderately acidic TME, achieve tumor‐specific MLT. Additionally, iron‐mediated Fenton reaction produces reactive oxygen species that augment oxidative stress, ultimately leading ferroptosis, whereas MLT‐induced membrane disruption promotes immunogenic cell death activate system. In combination with checkpoint inhibitor anti‐PD‐L1, this nanodrug elicits potent antitumor responses, facilitating infiltration effector T cells enhancing systemic immunity suppress both distant tumors. This study demonstrates tremendous potential nanoscale self‐destructive for targeted transport controlled reveals promoting effect combined ferroptosis cancer immunotherapy.