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Updated: Aug 26, 2025
Affordable Oxygen Microscopy-Assisted Biofabrication of Multicellular Spheroids
Published on: April 6, 2022
Biomimetic cell membrane-coated glucose/oxygen-exhausting nanoreactor for remodeling tumor microenvironment in
Haoyu Guo1, Weiyue Zhang2, Lutong Wang1
1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Abstract:
Hypoxia is a common feature within many types of solid tumors, which is closely associated with limited efficacy for tumor therapies. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in tumor-targeting and penetrating drug delivery systems in urgent need. Here, glucose oxidase (GOX) and hypoxia-activated prodrug tirapazamine (TPZ) are loaded into photothermal conversion agent polydopamine (PDA) as the glucose/oxygen-exhausting nanoreactor named PGT. We further construct a tumor cell membrane-coated nanovesicle for the targeted delivery of PGT. This biomimetic nanovesicle exhibits significantly improved tumor-targeting and tumor-penetrating abilities. After internalization by the tumor cells, the loaded drug is quickly released in response to near-infrared (NIR) laser. The PGT nanoreactor can exhaust glucose and oxygen, and further enhance hypoxia within tumor, which efficiently inhibits hypoxic tumor by combining starvation therapy and hypoxia-activated chemotherapy. Mechanically, it is revealed that the nanoreactor significantly increases hypoxia level and downregulates the expression of hypoxia-inhibitory factor-1α (HIF-1α), thereby promoting T cell activation and macrophage polarization to remodel tumor immunosuppressive microenvironment. Therefore, this tumor microenvironment-regulable nanoreactor with sustainable and cascade targeted starvation-chemotherapy provides a novel insight into the treatment of hypoxic tumor.
Insights
Researchers developed a novel nanoreactor that targets and penetrates solid tumors. This therapy depletes glucose and oxygen, enhancing hypoxia for combined starvation and chemotherapy, and remodels the tumor microenvironment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Solid tumors frequently exhibit hypoxia, correlating with reduced therapeutic effectiveness.
- Hypoxic tumor cells, distant from blood vessels, pose challenges for drug delivery systems.
Purpose of the Study:
- To develop a tumor-targeting and penetrating nanoreactor for enhanced hypoxic tumor therapy.
- To investigate the combined effects of starvation therapy and hypoxia-activated chemotherapy.
Main Methods:
- Glucose oxidase (GOX) and tirapazamine (TPZ) were loaded into polydopamine (PDA) to create a nanoreactor (PGT).
- A tumor cell membrane-coated nanovesicle was engineered for targeted PGT delivery.
- Near-infrared (NIR) laser was used for drug release and to induce photothermal effects.
Main Results:
- The nanovesicle demonstrated improved tumor targeting and penetration.
- PGT nanoreactors depleted glucose and oxygen, intensifying tumor hypoxia.
- This approach combined starvation therapy and hypoxia-activated chemotherapy, inhibiting tumor growth.
- Downregulation of hypoxia-inducible factor-1α (HIF-1α) was observed, promoting T cell activation and macrophage polarization.
Conclusions:
- The developed nanoreactor effectively treats hypoxic tumors by combining starvation and chemotherapy.
- This strategy remodels the tumor microenvironment, overcoming immunosuppression.
- The nanoreactor offers a novel approach for treating challenging hypoxic tumors.
