An Implantable Depot That Can Generate Oxygen in Situ for Overcoming Hypoxia-Induced Resistance to Anticancer Drugs in Chemotherapy
Abstract
In the absence of adequate oxygen, cancer cells that are grown in hypoxic solid tumors resist treatment using antitumor drugs (such as doxorubicin, DOX), owing to their attenuated intracellular production of reactive oxygen species (ROS). Hyperbaric oxygen (HBO) therapy favorably improves oxygen transport to the hypoxic tumor tissues, thereby increasing the sensitivity of tumor cells to DOX. However, the use of HBO with DOX potentiates the ROS-mediated cytotoxicity of the drug toward normal tissues. In this work, we hypothesize that regional oxygen treatment by an implanted oxygen-generating depot may enhance the cytotoxicity of DOX against malignant tissues in a highly site-specific manner, without raising systemic oxygen levels. Upon implantation close to the tumor, the oxygen-generating depot reacts with the interstitial medium to produce oxygen in situ, effectively shrinking the hypoxic regions in the tumor tissues. Increasing the local availability of oxygen causes the cytotoxicity of DOX that is accumulated in the tumors to be significantly enhanced by the elevated production of ROS, ultimately allaying the hypoxia-induced DOX resistance in solid malignancies. Importantly, this enhancement of cytotoxicity is limited to the site of the tumors, and this feature of the system that is proposed herein is unique.
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In situ generation of oxygen using catalase is attractive because it is self-responsive to H2O2 and does not require pre-treatment with O2.
“Specifically, in situ generation of oxygen using catalase as an enzyme is attractive because it is self-responsive to hydrogen peroxide (H2O2) and does not require pre-treatment with oxygen ( 3 O2).18,19,24”
From Catalase-Integrated Hyaluronic Acid as Nanocarriers for Enhanced Photodynamic Therapy in Solid Tumor (2019) · cites this paper as [18]
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- Authors
- Huang, C.-C., Chia, W.-T., Chung, M.-F., Lin, K.-J., Hsiao, C.-W., Jin, C., Lim, W.-H., Chen, C.-C., & Sung, H.-W.
- Affiliations
- National Tsing Hua University (TW)
- National Taiwan University Hospital (TW)
- Chang Gung Memorial Hospital (TW)
- Corresponding author
- Sung, Hsing-Wen
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-04-13
- Volume
- 138
- Issue
- 16
- Pages
- 5222-5225
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2320182137
- Cited by
- 372
- References
- 18
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 39 · 2023: 37 · 2022: 47 · 2021: 46 · 2020: 64 · 2019: 46 · 2018: 45 · 2017: 17 · 2016: 7
- FWCI
- 18.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology (MOST 104-2314-B-007-001-MY3)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- in situ oxygen generation, tumor hypoxia, doxorubicin resistance, hyperbaric oxygen therapy, reactive oxygen species, chemoresistance, solid tumors, drug cytotoxicity
- MeSH terms
- Carbonic Anhydrase IX, Tumor Hypoxia, Animals, Antigens, Neoplasm, Antineoplastic Agents, Calcium Chloride, Catalase, Doxorubicin, Drug Implants, Humans, Hyperbaric Oxygenation, Mice, Nude, Oxygen, Peroxides, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Positron-Emission Tomography
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