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Updated: Feb 14, 2026

Production and Detection of Reactive Oxygen Species ROS in Cancers
Published on: November 21, 2011
In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination
Chao Wang1,2, Jinqiang Wang1,2, Xudong Zhang1,2
1Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA.
Abstract:
Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection.
Insights
This study introduces a novel scaffold delivering gemcitabine and anti-PD-L1 therapy directly to tumors. This approach enhances anti-tumor immunity and promotes tumor regression, preventing recurrence in preclinical models.
Area of Science:
- Biomedical Engineering
- Immunotherapy
- Drug Delivery Systems
Background:
- Low-immunogenic tumors exhibit poor response to immune checkpoint blockade (ICB) therapies targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway.
- Immune checkpoint blockade (ICB) therapy can lead to significant side effects in responding patients.
Purpose of the Study:
- To engineer a localized therapeutic delivery system combining chemotherapy and immunotherapy for enhanced anti-tumor immune response.
- To develop a novel scaffold for in situ formation and programmed release of gemcitabine (GEM) and an anti-PD-L1 antibody (aPDL1).
Main Methods:
- Fabrication of a reactive oxygen species (ROS)-degradable hydrogel scaffold for controlled drug release within the tumor microenvironment (TME).
- In situ administration of the scaffold to release GEM and aPDL1 with distinct release kinetics.
- Evaluation of the scaffold's efficacy in promoting immunogenic tumor phenotype and immune-mediated tumor regression in tumor-bearing mice.
Main Results:
- The engineered aPDL1-GEM scaffold successfully elicited an immunogenic tumor phenotype in vivo.
- The scaffold demonstrated significant immune-mediated tumor regression in preclinical models.
- Treatment with the aPDL1-GEM scaffold prevented tumor recurrence after primary tumor resection.
Conclusions:
- The developed ROS-degradable hydrogel scaffold offers a promising strategy for localized delivery of combination therapy (GEM and aPDL1).
- This localized approach enhances anti-tumor immunity and achieves durable tumor regression, highlighting its potential for treating low-immunogenic tumors and preventing recurrence.
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