Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity

Dan Zhang

doi:10.1016/j.apsb.2026.07.040

Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity

2026-07-29

0

OA

AI

D

Dan Zhang

A

Anxian Chen

H

Haimeng Huang

W

Wenjing Li

Q

Qili Huang

H

Hongzhong Chen

J

Jiaxing Zhang

L

Li Yang *

C

Caijun Sun *

X

Xiaowei Zeng *

DOI：10.1016/j.apsb.2026.07.040

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Abstract

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Immunogenic cell death (ICD) provides a promising strategy for cancer treatment by stimulating anti-tumor immunity. However, single ICD inducers often induce 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.

Keywords:

Immunogenic cell death

Stimulate-and-retain strategy

Antigen reservoir

Oncolytic virus

Oxaliplatin

Cancer immunotherapy

Bioadhesive hydrogel

Damage-associated molecular patterns

Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity

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