Cited by 220Hydrogels: synthesis, properties, applicationsCancer Immunotherapy and BiomarkersNanoplatforms for cancer theranostics

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A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade

Ruan, Huitong, Hu, Quanyin, Wen, Di, Chen, Qian, Chen, Guojun, Lu, Yifei, Wang, Jinqiang, Cheng, Hao, Lu, Weiyue, Gu, Zhen·2019·Advanced Materials

DOI 10.1002/adma.201806957

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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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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: Ruan, Huitong
Hu, Quanyin
Wen, Di
Chen, Qian
Chen, Guojun
Wang, Jinqiang
Cheng, Hao
Lu, Weiyue
Gu, Zhen
Venue: Advanced Materials
Publisher: Wiley
Published: 2019-03-11
Volume: 31
Issue: 17
Pages: e1806957-e1806957
ISSN: 0935-9648 (ISSN-L)
1521-4095
DOI: 10.1002/adma.201806957
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: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
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: Physical Sciences › Materials Science › Biomaterials › 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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A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade

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