Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity.
- 1State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
- 2School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
- 3Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
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.
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BibTeX
@article{zhang2026stimulateandretain,
title = {{Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity.}},
author = {Dan Zhang and Anxian Chen and Haimeng Huang and Wenjing Li and Qili Huang and Hongzhong Chen and Jiaxing Zhang and Li Yang and Caijun Sun and Xiaowei Zeng},
journal = {Acta pharmaceutica Sinica. B},
year = {2026},
month = jul,
doi = {10.1016/j.apsb.2026.07.040},
url = {https://europepmc.org/article/MED/42948701},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Stimulate-and-retain hydrogel strategy integrating oncolytic virus and oxaliplatin for dual ICD-inducing antitumor immunity.
AU - Dan Zhang
AU - Anxian Chen
AU - Haimeng Huang
AU - Wenjing Li
AU - Qili Huang
AU - Hongzhong Chen
AU - Jiaxing Zhang
AU - Li Yang
AU - Caijun Sun
AU - Xiaowei Zeng
PY - 2026
DA - 2026/07/29
JO - Acta pharmaceutica Sinica. B
DO - 10.1016/j.apsb.2026.07.040
UR - https://europepmc.org/article/MED/42948701
AB - 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.
SN - 2211-3835
SN - 2211-3843
ER -