In Situ Formed Nanocomposite Hydrogel Improve Local Delivery of Antiangiogenic Agents and Immune Checkpoint Inhibitor for Cervical Carcinoma Therapy

Abstract

Immune checkpoint blockade targeting the programmed cell death protein‐1 (PD‐1)/ligand (PD‐L1) axis has emerged as a promising therapeutic strategy for cervical carcinoma. However, its clinical application remains limited by the immunosuppressive tumor microenvironment (TME) and poor targeting efficiency, particularly in solid tumors. To address these challenges, a nanocomposite hydrogel system (Apa/BPNPs@Gel) is developed by encapsulating PD‐L1 inhibitor BMS202 nanoparticles coated with polyvinyl alcohol (BPNPs) into a polyvinyl alcohol/alginate hybrid hydrogel. This in situ formed hydrogel exhibits favorable biocompatibility and reactive oxygen species‐dependent sequential drug release. Initially, the antiangiogenic agent apatinib (Apa) is released to alleviate tumor hypoxia through vascular normalization and enhance PD‐L1 suppression, priming the TME for subsequent anti‐PD(L)1 therapy. The hydrogel framework extends the residence time of BMS202 (a skeleton component), improving therapeutic efficacy. Notably, in preclinical cervical carcinoma models, Apa/BPNPs@Gel mediated combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor‐suppressed CD8+ T cells. Hence, this locally administrable hydrogel offers a versatile platform to modulate the immunosuppressive TME and enhance immunotherapeutic outcomes.