Journal article
A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade
Advanced materials (Weinheim), v 31(17)
25 Apr 2019
PMID: 30856290
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 (CaCO3 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.
A dual bioresponsive drug delivery depot is engineered, which can respond to the acidic pH and reactive oxygen species within the tumor microenvironment (TME), for codelivery of anti‐PD1 antibody and Zebularine, an epigenetic modulator. It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, reverses immunosuppressive TME, and enhances the antitumor immune response.
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Details
- Title
- A Dual‐Bioresponsive Drug‐Delivery Depot for Combination of Epigenetic Modulation and Immune Checkpoint Blockade
- Creators
- Huitong Ruan - University of California, Los AngelesQuanyin Hu - University of California, Los AngelesDi Wen - University of California, Los AngelesQian Chen - University of California, Los AngelesGuojun Chen - University of California, Los AngelesYifei Lu - University of California, Los AngelesJinqiang Wang - University of California, Los AngelesHao Cheng - Drexel UniversityWeiyue Lu - Fudan UniversityZhen Gu - University of California, Los Angeles
- Publication Details
- Advanced materials (Weinheim), v 31(17)
- Publisher
- Wiley
- Number of pages
- 8
- Grant note
- National Natural Science Foundation of China (81690263) China Scholarship Council Alfred P. Sloan Foundation UNC Chapel Hill/NC state
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:000465600000006
- Scopus ID
- 2-s2.0-85062791754
- Other Identifier
- 991019168309604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Chemistry, Physical
- Materials Science, Multidisciplinary
- Nanoscience & Nanotechnology
- Physics, Applied
- Physics, Condensed Matter