Curcumin‐Embedded Magnesium‐Polyphenol Network Hydrogel for Dual Delivery of aPD1 and Promotion of Pleural Sealing in Lung Cancer Immunotherapy

ABSTRACT Lung cancer remains the leading cause of cancer‐related mortality worldwide, with surgically inoperable cases posing a significant clinical challenge. Although microwave ablation (MWA) is a viable treatment option for non‐surgical patients, its effectiveness is often compromised by substantial complications and inadequate prevention of tumor recurrence or progression. To address these limitations, we developed a multifunctional hydrogel system (aPD1@Cur‐Mg/GH) that integrates antitumor immunomodulation with pleural sealing capabilities. This hydrogel combines a gelatin methacryloyl (GelMA)/o‐nitrobenzyl alcohol‐modified hyaluronate (HANB) matrix (GH) with an aPD1‐loaded curcumin‐embedded magnesium‐polyphenol network (Cur‐Mg/aPD1). By utilizing the photocrosslinking properties of GelMA and HANB, the aPD1@Cur‐Mg/GH hydrogel forms a robust, adhesive, and compression‐resistant structure that is ideal for pleural sealing and tissue repair. Upon degradation, the hydrogel releases Mg 2 + ions and curcumin, which promote M1 macrophage polarization and enhance CD8 + T cell infiltration, thereby synergizing with MWA to improve the efficacy of immune checkpoint blockade therapy. Our findings demonstrate that this dual‐functional hydrogel significantly modulates the post‐ablation tumor immune microenvironment and presents a promising strategy for enhancing lung cancer immunotherapy following MWA.