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.