Intraoperative Cavity Local Delivery System with NETs‐Specific Drug Release for Post‐Breast Cancer Surgery Recurrence Correction

Abstract

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors‐β (TGF‐β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio‐safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF‐β at tumor‐resection sites, whose unique mechanism for local TGF‐β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti‐TGF‐β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF‐β and related indicators, impeding epithelial‐mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.