dioxygen

Overview

Dioxygen (O₂) is a diatomic molecule composed of two bonded oxygen atoms and represents the primary electron acceptor in aerobic metabolism across most living organisms. In normal physiology, dioxygen is essential for cellular respiration, serving as the terminal electron acceptor in the mitochondrial electron transport chain and enabling efficient adenosine triphosphate (ATP) production. However, in pathological conditions such as solid tumors, hypoxic microenvironments develop due to insufficient vascularization and high metabolic demand, creating regions of inadequate oxygen availability. These hypoxic regions have emerged as a significant barrier to therapeutic efficacy, as many treatment modalities—including photodynamic therapy, immunotherapy, and ferroptosis-based approaches—depend on adequate oxygen tension for optimal function.

The biomedical significance of oxygen has expanded in recent years with the development of engineered platforms designed to generate, deliver, or sense molecular oxygen at the site of disease. These approaches recognize that traditional systemic oxygen supplementation strategies face limitations in achieving precise spatiotemporal control and adequate penetration into heterogeneous tissue microenvironments. As a result, local oxygen generation and delivery have become focal points in developing next-generation therapeutics for cancer, wound healing, and inflammatory conditions.

Role in Recent Research

Recent biomedical research has positioned dioxygen as a critical therapeutic target, particularly in oncology, where tumor hypoxia represents a major impediment to treatment success. A recurring theme across multiple studies involves the development of nanomaterial-based platforms capable of generating oxygen in situ or enriching oxygen availability at the tumor microenvironment.

Oxygen Alleviation of Tumor Hypoxia and Enhancement of Immunotherapy

Several studies have demonstrated that alleviating intratumoral hypoxia through oxygen generation reverses immunosuppression and enhances the efficacy of immune-dependent therapies. In one approach, a copper-based nanoplatform was employed to synergistically augment cuproptosis and anti-metastatic immunity in breast cancer; platinum nanodots incorporated into this platform exhibited catalase-like activity, decomposing hydrogen peroxide into molecular oxygen while simultaneously alleviating hypoxia and suppressing hypoxia-inducible factor-1α (HIF-1α), thereby enhancing mitochondrial susceptibility to copper-induced lethality. Similarly, a multifunctional bimetallic metal-organic framework nanozyme platform regulated oxygen release alongside hydroxyl radical generation and glutathione depletion through multi-enzyme-like catalytic activities, effectively alleviating hypoxia and inducing apoptosis and ferroptosis in tumor cells. A calcium peroxide nanoplatform achieved analogous benefits, with studies noting that oxygen alleviates hypoxia to reverse immunosuppression and enhance the efficacy of oxygen-dependent therapies. Emerging nanoplatforms generally face the challenge of achieving precise oxygen regulation in the complex tumor microenvironment, as traditional supplementation strategies are limited by spatiotemporal heterogeneity of tumor tissues, low delivery efficiency, and biosafety concerns.

Oxygen Generation via Catalytic Nanomaterials

catalase-based nanomaterials have emerged as effective tools for in situ oxygen generation. A biomimetic catalase-engineered black phosphorus nanosheet construct efficiently catalyzed endogenous hydrogen peroxide into oxygen, thereby relieving intratumoral hypoxia in hepatocellular carcinoma. In diabetic wound healing, a glucose-triggered self-perpetuating catalytic cascade within GOx@CuO₂ nanoreactors generated oxygen while simultaneously alleviating oxidative stress and promoting angiogenesis. A cascade nanozyme hydrogel dressing engineered to release both nitric oxide and oxygen enhanced neuro-vascular coupling and immunomodulation for accelerated diabetic wound repair.

Oxygen Enrichment in Photodynamic Therapy

Photodynamic therapy (PDT) fundamentally depends on oxygen availability for singlet oxygen (¹O₂) generation. Perfluoroalkylated amphiphilic porphyrin nanomicelles were developed to enrich and deliver oxygen while achieving enhanced photosensitizing activity for singlet oxygen generation. A photoresponsive carbon dot hydrogel demonstrated the capacity to generate molecular oxygen in tumor hypoxia regions, thereby supporting the photodynamic mechanism.

Biosensing Applications

Beyond therapeutic applications, dioxygen has become a measurable biomarker in biosensing platforms. In vitro testing of granular hydrogels loaded with oxygen-biosensing microdomains demonstrated responsiveness across a physiologically relevant range from 0% to 21% oxygen. Additionally, metal-free room temperature phosphorescence (RTP) materials were developed specifically for aqueous environments to address challenges in maintaining stability against water and oxygen, expanding the toolkit for diagnostic oxygen monitoring.

Molecular Modeling of Oxygen Transport

Mathematical modeling of peritoneal dialysis has integrated descriptions of oxygen and carbon dioxide transport across central circulation and tissues, predicting changes in acid-base equilibrium driven by transport processes. This systems-level approach to understanding oxygen distribution and utilization reflects the fundamental importance of dioxygen in maintaining cellular and organ-level homeostasis.

Together, these studies underscore dioxygen's dual role in biomedical science: as a critical limiting factor in disease pathophysiology (particularly in hypoxic disease states) and as an actively engineered therapeutic agent capable of reversing pathological conditions and enhancing the efficacy of immunotherapies, photodynamic treatments, and wound-healing interventions.

Key Publications

• NEWJun Biomedical publication details. (PubMed Database, 2026, PMID 42300531)
• NEWJun Biomedical publication details. (PubMed Database, 2026, PMID 42132802)
• NEWJun Biomedical publication details. (PubMed Database, 2026, PMID 42295119)
• Jun Biomedical publication details. (PubMed Database, 2026, PMID 42401598)
• Jun Biomedical publication details. (PubMed Database, 2026, PMID 42148957)
• Jun Biomedical publication details. (PubMed Database, 2026, PMID 42390183)
• Feb Glucose-triggered self-perpetuating catalytic cascade in GOx@CuO2 nanoreactors for treating bacteria-infected diabetic wounds. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41759381): "This alleviates oxidative stress and promote angiogenesis, forming an adaptive synergistic therapeutic cycle of 'antibacterial-promoting healing'."
• Feb A multifunctional bimetallic MOF nanozyme orchestrating ferroptosis-apoptosis synergy for enhanced gastric tumor immunotherapy. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41763117): "This novel nanozyme platform-designated as 5-FUZIF-8@FeaPD-L1-effectively regulated oxygen release, hydroxyl radical generation, and glutathione depletion through multi-enzyme-like catalytic activities, which alleviated hypoxia and induced apoptosis and ferroptosis in the tumor cells."
• Jun Biomedical publication details. (PubMed Database, 2026, PMID 42328680)
• Jun Biomedical publication details. (PubMed Database, 2026, PMID 42325397)