A self-initiating battery-like hydrogel for autonomous pH normalization and immune activation in postoperative tumor therapy.

Abstract

Postoperative recurrence and metastasis remain major causes of cancer mortality, capitally driven by the inevitably acidic niche during surgical wound repair. However, current pH-regulating strategies show transient efficacy and remain passively responsiveness, failing to accommodate the progressive and fluctuating acidification of the postoperative microenvironment. Here, we report an implantable self-initiating battery-like hydrogel that can autonomously sense pH changes and persistently neutralize acidosis through well-designed internal redox reactions. The hydrogel incorporates Fe³⁺-quercetin as the initiating redox unit and conductive poly(3,4-ethylenedioxythiophene) as the electron mediator, enabling sustained quercetin-quinonoid species cycling with H⁺ consumption. It provided a broad pH modulation window that covers postoperative pH fluctuation (pH 5.3-6.8) and stabilizes it to neutrality, preventing the formation of pro-recurrence acidic niche. Meanwhile, embedded homoharringtonine-loaded nanoparticles were encapsulated in the hydrogel to promote M2 to M1 macrophages polarization. Fortunately, this system eliminates residual tumor cells and remodels the immunosuppressive microenvironment, resulting in ∼95% suppression of tumor recurrence, while preventing metastasis and establishing durable immune memory. With biocompatible components and flexible architecture suitable for irregular tumor beds, this battery-like hydrogel serves as a promising immunotherapeutic platform for postoperative tumor management.