An injectable gel activated by low-dose X-rays delivers sustained antibacterial effects in deep tissue by generating reactive oxygen species, offering a non-antibiotic strategy for hard-to-treat infections.
(Nanowerk Spotlight) Medicine still has no reliable way to eliminate a bacterial infection once it is embedded deep in tissue and shielded from circulation. These infections often appear after surgery, trauma, or internal injury. They persist not because the bacteria are highly resistant, but because the drugs meant to eliminate them cannot reach the site in effective concentrations. Local delivery is inconsistent. Immune access is limited. Infected abscesses and biofilms can survive in a protected niche, which may require surgical removal or ongoing treatment. Some infections never fully resolve.
This is not a rare or unusual failure. It reflects a structural limitation in the way antimicrobial therapies are delivered. The danger increases as resistance to antibiotics becomes more common. In many cases, even bacteria that are technically sensitive to treatment will persist if the drug does not reach them. The core issue is spatial control. There is still no reliable way to activate a strong, localized antibacterial effect inside living tissue without harming surrounding cells.
Efforts to solve this problem have produced a range of experimental strategies. Researchers have explored methods based on heat, ultrasound, electrical stimulation, and light. Light-activated therapies, in particular, have shown promise because they can produce highly localized chemical effects using compounds that remain inactive until exposed to external energy.
However, visible and near-infrared light cannot penetrate more than a few millimeters through tissue. X-rays can, but most systems that respond to X-rays either stop working as soon as the radiation ends, require high doses, or involve complicated designs that are difficult to implement clinically.
Schematic representation of the development of the X-ray-activated SAO25-AO@gel platform, and b) its application for imaging-guided deep-seated antibacterial therapy through a robust ROS storm generation mechanism. (Image: Reprinted with permission by Wiley-VCH Verlag) (click on image to enlarge)
The researchers developed an injectable gel that combines X-ray responsiveness with chemical persistence. Once activated by a low dose of X-rays, the material generates reactive oxygen species that kill bacteria through oxidative stress. These effects continue after the radiation source is removed, offering a way to target infections in tissue volumes that are otherwise inaccessible to drugs or light.
The system is built from two key components. The first is a strontium aluminate phosphor doped with europium and dysprosium. It emits visible light when exposed to X-rays and continues to emit for hours after the exposure ends. This property, known as persistent luminescence, is rare among solid-state materials and provides an internal light source without the need for repeated external activation.
The second component is acridine orange, a molecule that produces singlet oxygen when exposed to visible light. Singlet oxygen is a reactive form of oxygen that damages cell membranes, proteins, and DNA. It is widely used in photodynamic therapy for cancer and microbial infections.
These two materials are embedded in a sodium alginate hydrogel that provides a biocompatible matrix and holds them in place at the target site. When the gel is exposed to X-rays, several processes occur at once. The strontium aluminate generates superoxide, hydroxyl radicals, and hydrogen peroxide through direct chemical reactions.
It also emits light that activates acridine orange, which in turn produces singlet oxygen. Even after the X-ray source is switched off, the material continues to emit light, allowing the acridine orange to remain chemically active. The result is a sustained release of reactive oxygen species through multiple overlapping mechanisms.
Laboratory tests showed that this system was effective against both Staphylococcus aureus and Escherichia coli, two common and clinically significant pathogens. After eight minutes of X-ray exposure, bacterial survival dropped by more than 99 percent.
The same treatment disrupted more than 90 percent of preformed biofilms, which are normally difficult to penetrate using either antibiotics or physical disruption. Microscopy revealed extensive membrane damage and structural collapse in treated cells, consistent with the expected effects of oxidative stress.
The team also tested the system in tissue. In a pork model, the gel was applied beneath 1.5 centimeters of muscle tissue, with bacteria layered on the far side. Even through this depth, the X-ray exposure activated the gel and reduced bacterial counts by nearly 99 percent. This confirms that the material can be triggered under conditions where light-based therapies fail due to poor penetration.
For in vivo applications, the researchers replaced the sodium alginate gel with Pluronic F127, a thermosensitive polymer that remains liquid at room temperature but solidifies at body temperature. This allows the material to be injected as a liquid and retained at the infection site once it gels.
In a mouse model of deep muscle abscess, a single injection followed by X-ray exposure significantly reduced bacterial load and abscess size. Treated tissue showed increased collagen deposition and reduced inflammation, with no evidence of damage to surrounding organs.
The platform was also tested for biocompatibility. It showed low toxicity in cultured skin and fibroblast cells, minimal hemolysis, and no visible degradation or phase separation after storage. It remained stable through repeated cycles of activation and retained its structural integrity over several days.
The key advance in this study is not just the ability to kill bacteria using X-ray-activated chemistry. It is the design of a system that combines direct chemical reactivity, internal light emission, and delayed activation in a single, injectable material. Each mechanism reinforces the others.
The use of multiple reactive oxygen species increases the range of biological targets and reduces the chance of bacterial survival. Because these species act through non-specific oxidative damage, they are less likely to trigger or succumb to resistance.
Although the system has not yet been tested in humans, and its long-term safety and clearance profile remain open questions, it represents a shift in the way local antibacterial therapy can be delivered. It does not rely on precise targeting at the molecular level or on continuous drug release. Instead, it uses materials that convert physical energy into sustained chemical action inside tissue.
The study provides a functional example of how spatial control, chemical persistence, and clinically relevant activation can be combined in a single therapeutic platform. It offers a path forward for treating infections in places medicine cannot currently reach.
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