An implantable zinc magnesium battery generates hydrogen and removes oxygen inside tumors, triggering a hypoxia-activated drug and achieving strong, localized tumor suppression in mice.
(Nanowerk Spotlight) Every treatment that attacks cancer also risks harming the body that carries it. Drugs circulate through the bloodstream and strike healthy cells along with malignant ones. Radiation can burn tissue that surrounds a tumor, and heat-based therapies often spread beyond their targets. Modern medicine can now aim more precisely, yet true chemical precision remains elusive. The central challenge is to destroy malignant cells without collateral damage and to do it at the molecular level inside the complex chemistry of living tissue.
Some scientists have tried to solve that problem by turning the tumor’s own biology into an ally. Many solid tumors grow in oxygen-poor conditions, a state called hypoxia, which weakens their normal metabolism and could in theory make them selectively vulnerable. Certain drugs, known as hypoxia activated prodrugs, exploit that feature by switching on only when oxygen levels drop.
The idea is elegant: the drug stays harmless in healthy tissue and becomes toxic only in the oxygen starved pockets of a tumor. In practice, though, tumors are inconsistent. Some are not hypoxic enough, and others shift back to normal oxygen levels before the drug can act.
Another experimental route uses therapeutic gases such as hydrogen. Hydrogen can modulate oxidative stress and alter tumor metabolism, but it is difficult to hold inside tissue long enough to have a sustained effect. Gas molecules leak away through blood and membranes before they can reach stable concentrations. Efforts to carry hydrogen into tumors with nanoparticles or to generate it with catalysts triggered by light or acidity have shown limited reach and short duration.
What has changed is materials science. Biodegradable metals such as zinc and magnesium can safely corrode inside the body, while thin carbon based electrodes and microscale batteries now make it possible to build small implants that generate chemical reactions without external power. These advances have created an opening: instead of transporting gases or manipulating oxygen with drugs, it may be possible to make the chemistry happen right where it is needed.
That question anchors a study published in Advanced Functional Materials (“Bioimplantable Bifunctional Zinc/Magnesium–Oxygen Battery for Synergistic Gas Therapy and Hypoxia‐Activated Chemotherapy”). It describes a tiny implant that behaves like a self-contained electrochemical cell. When placed inside a tumor, it continuously produces hydrogen and consumes oxygen, reshaping the local environment so that gas therapy and drug activation can reinforce each other. The research tests whether a device built from simple, biocompatible materials can create this double effect safely inside living tissue.
The device consists of a zinc magnesium alloy anode and a cathode made of a thin carbon nanotube film coated with platinum. A porous cellulose sheet separates them, and the surrounding body fluid serves as the electrolyte. When the circuit is closed, the metal anode oxidizes, releasing electrons that drive two reactions. Water molecules are reduced to produce hydrogen gas, and oxygen at the cathode is converted into hydroxide ions through what chemists call the oxygen reduction reaction. In simple terms, one side of the implant makes hydrogen while the other side consumes oxygen. This coupling forms the basis of the intended therapy.
Bifunctional zinc/magnesium–oxygen (Zn/Mg–O2) battery for synergistic gas therapy and hypoxia-activated chemotherapy. a) Schematic illustration of the Zn/Mg–O2 battery generating hydrogen and consuming oxygen at the tumour site. b,c) Schematic representations of hydrogen therapy and enhanced chemo-/immunotherapy strategies enabled by the Zn/Mg–O2 battery. (Image: Reprinted with permission by Wiley-VCH Verlag) (click on image to enlarge)
The researchers confirmed that the platinum coated carbon film actively reduced oxygen whenever it was exposed to air saturated fluid, verifying that it performed its expected catalytic role. On the metal side, both zinc and magnesium contributed to hydrogen generation as they reacted with water.
Tests using chemical dyes and gas analysis showed steady hydrogen release for at least seven days, with higher rates under mildly acidic conditions typical of tumor tissue. Within sealed solutions, oxygen concentration fell rapidly and reached very low levels in a few hours, staying depleted for more than twelve hours before diffusion restored balance.
These results demonstrated that a small implantable cell could simultaneously create hydrogen and sustain hypoxia.
Cell culture experiments revealed how those environmental changes affected cancer cells. When exposed to the discharged device, tumor cells lost much of their mitochondrial membrane potential, an indicator that their energy producing machinery was failing. Measurements of adenosine triphosphate, the molecule that stores and transfers energy inside cells, dropped to about one third of normal levels, while extracellular ATP rose, a sign of disrupted metabolism and possible cell damage.
Fluorescent probes showed that nearly half of the cells entered a deeply hypoxic state. When tirapazamine was added under these conditions, the production of reactive oxygen species increased sharply, meaning the drug was successfully activated by the oxygen poor environment.
Cell viability assays reflected the combined effect. Tirapazamine by itself caused limited harm in normal oxygen conditions. The device, even without electrical discharge, reduced cell survival modestly because corrosion still produced some hydrogen. When fully active, it caused much stronger cell death. The combination of the operating device and tirapazamine proved most potent, killing more than eighty percent of cells in culture.
Protein analyses showed activation of apoptosis, the programmed cell death pathway, with clear signs such as increased levels of Caspase 3 and BAX. The treatment also induced markers of immunogenic cell death, including surface exposure of calreticulin and release of nuclear protein HMGB1, both of which can alert the immune system to destroyed tumor cells.
Testing then moved to a mouse model of triple negative breast cancer. The researchers implanted the small battery directly into established tumors and administered a single intravenous dose of tirapazamine in the combination group. Imaging with ultrasound revealed persistent microbubble signals at the implant site for more than a week, confirming ongoing hydrogen production.
Temperature measurements showed minimal heating, indicating that the reaction did not damage tissue through excess warmth. Immunostaining for HIF 1α, a protein that accumulates under low oxygen, revealed much stronger signals in tumors with active devices, confirming the creation of a hypoxic microenvironment.
Therapeutic results were striking within the bounds of the animal model. Mice treated with tirapazamine alone showed only modest slowing of tumor growth. An inactive implant gave moderate benefit. An active implant alone suppressed tumor volume by more than eighty percent over two weeks.
The combination of the active device and tirapazamine nearly eliminated the tumors during the observation period. Average tumor mass dropped by more than ninety percent relative to controls, and body weight remained stable, suggesting limited systemic toxicity. Tissue examination found extensive tumor necrosis but no significant damage in major organs.
Analysis of immune markers supported the cell culture findings. The treated mice displayed higher counts of CD4 positive and CD8 positive T cells in both spleen and tumor tissue, along with elevated levels of signaling molecules such as tumor necrosis factor alpha, interleukin 6, and interferon gamma. These patterns imply that local destruction of tumor cells through hydrogen exposure and drug activation may have stimulated an immune response capable of contributing to tumor control.
The materials chosen for the device point toward realistic translation. Zinc and magnesium alloys are already studied as biodegradable metals for temporary implants. Carbon nanotube electrodes and thin platinum coatings are familiar to biomedical engineers. A cellulose separator is biocompatible and simple to manufacture. Because body fluid serves as the electrolyte, there is no need for a separate liquid or gel.
The device operates autonomously without external wires or power supplies. Adjusting its size or alloy composition can tune how much gas it produces and how quickly oxygen is consumed. The current design sustains its reactions for hours to days, matching the time frame needed for prodrug activation.
Although these findings are confined to laboratory and mouse experiments, they show that an implant can actively change the chemistry of its surroundings in a controlled way to support combined therapies. A future version could be paired with other hypoxia activated drugs or adapted for tumors that respond to controlled oxygen modulation.
The concept could also enhance radiation or immune treatments that depend on specific oxygen or redox states. What stands out is that the device works through simple, well understood reactions, powered only by materials that safely degrade in the body. That simplicity may help the idea move from small animals toward clinical exploration.
This work demonstrates that a bioimplantable zinc magnesium oxygen battery can act as both a hydrogen generator and an oxygen consumer. In mice, it reshapes the tumor environment to enable two simultaneous modes of attack: hydrogen induced metabolic disruption and activation of a hypoxia sensitive drug. Within the limits of the study, the system delivers strong antitumor effects while showing acceptable safety. It represents a practical example of how electrochemical design can manipulate local biochemistry for therapeutic gain.
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Ji Liu (Southern University of Science and Technology)
, 0000-0001-7171-405X corresponding author
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