A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade
Abstract
Patients with advanced melanoma that is of low tumor‐associated antigen (TAA) expression often respond poorly to PD‐1/PD‐L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti‐PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH‐sensitive calcium carbonate nanoparticles (CaCO 3 NPs), which are then encapsulated in the ROS‐responsive hydrogel together with Zeb (Zeb‐aPD1‐NPs‐Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10‐melanoma‐bearing mice.
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Accumulating evidence indicates that chemotherapy, radiotherapy, angiogenesis inhibitor, STING agonist, FMT, epigenetic modulators, or other immunomodulators could synergize α-PD-1/PD-L1, by enhancing cancer antigen release, APC function, or effector activity.
“Accumulating evidence indicates that chemotherapy, radiotherapy, angiogenesis inhibitor, stimulator of interferon genes (STING) agonist, fecal microbiota transplantation (FMT), epigenetic modulators, or other immunomodulators could synergize α-PD-1/PD-L1, by enhancing cancer antigen release, APC function, or effector activity [22–31].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [27]
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- Authors
- Ruan, H., Hu, Q., Wen, D., Chen, Q., Chen, G., Lu, Y., Wang, J., Cheng, H., Lu, W., & Gu, Z.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Department of Bioengineering University of California Los Angeles CA 90095 USA
- Drexel University (US)
- Fudan University (CN)
- Corresponding author
- Lu, Weiyue
- Gu, Zhen
- ORCID
- Venue
- Advanced Materials
- Publisher
- Wiley
- Published
- 2019-03-11
- Volume
- 31
- Issue
- 17
- Pages
- e1806957-e1806957
- ISSN
- 0935-9648 (ISSN-L)
- 1521-4095
- OpenAlex
- W2922000375
- Cited by
- 220
- References
- 55
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 31 · 2023: 32 · 2022: 40 · 2021: 38 · 2020: 39 · 2019: 17
- FWCI
- 11.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Advanced Materials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of North Carolina at Chapel Hill
- Alfred P. Sloan Foundation
- National Natural Science Foundation of China (81690263)
- China Scholarship Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- advanced melanoma, epigenetic modulation, zebularine, PD-1/PD-L1 blockade, anti-PD-1, ROS-responsive hydrogel, tumor microenvironment, tumor-associated antigen expression, immunosuppressive tumor microenvironment, combination immunotherapy, B16F10 melanoma
- MeSH terms
- Animals, Antibodies, Monoclonal, Antineoplastic Agents, Calcium Carbonate, Cytidine, Drug Therapy, Combination, Humans, Hydrogen-Ion Concentration, Immunosuppressive Agents, Immunotherapy, Melanoma, Drug Delivery Systems, Reactive Oxygen Species, Cell Line, Tumor, Nanoparticles, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized, Drug Liberation
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