Authors
Dan Zhang, Anxian Chen, Haimeng Huang, Wenjing Li, Qili Huang, Hongzhong Chen, Jiaxing Zhang, Li Yang, Caijun Sun, Xiaowei Zeng
Published in
Acta pharmaceutica Sinica. B. Volume 16. Issue 10. Pages 6943-6957. Epub Jul 29, 2026.
Abstract
Immunogenic cell death (ICD) provides a promising strategy for cancer treatment by stimulating anti-tumor immunity. However, single ICD inducers often elicit insufficient damage-associated molecular patterns (DAMPs), and the rapid clearance of these DAMPs at the tumor site further prevents sustained immune stimulation. To address these challenges, we developed a polyphenol-based bioadhesive hydrogel antigen reservoir functionalized with dopamine (DA) and loaded with dual ICD inducers. Specifically, thymidine kinase (tk)-deficient oncolytic vaccinia virus (VV, a type II ICD inducer) was combined with oxaliplatin (OXA, a type I ICD inducer), thereby enhancing direct tumor cytotoxicity and synergistically amplifying ICD through distinct mechanisms to promote robust DAMP release. Subsequently, the released DAMPs were captured and retained by the DA-functionalized hyaluronic acid-Pluronic® F127 hydrogel (HADP), forming an antigen reservoir at the tumor site. This synergistic "stimulate-and-retain" strategy not only augments ICD-mediated DAMP release but also prolongs their local availability to sustain immune stimulation. In murine models, the OXA-HADP@VV facilitated dendritic cell (DC) activation, increased IFN-γ +CD8+ T cell infiltration, and reduced regulatory T cells (Tregs), thereby achieving effective tumor suppression and strong anti-recurrence effects. Together, this dual ICD-inducing antigen reservoir provides a versatile platform for improving cancer immunotherapy.
PMID:
42948701
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.
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