Article Title: Terahertz Wave Desensitizes Ferroptosis by Inhibiting the Binding of Ferric Ions to Transferrin
Authors: Xiangji Li, Yangmei Li, Junxuan Xu, Xinlian Lu, Shixiang Ma, Lan Sun, Chao Chang, Li Min, Chunhai Fan
Published by: American Chemical Society, 2025
Recent groundbreaking research demonstrates that terahertz (THz) radiation at about 34.5 THz (equivalent to 8.7 μm in wavelength, or 34,500 GHz) can inhibit the binding between ferric ions (Fe³⁺) and transferrin (Tf), thereby desensitizing ferroptosis both in vitro and in vivo. Ferroptosis, a specialized form of cell death heavily reliant on iron and characterized by lipid peroxidation, plays a critical role in conditions such as cancer, intestinal ischemia–reperfusion injury, and various neurological disorders.
Traditional drug-based approaches to regulating transferrin risk disrupting the body’s overall iron homeostasis. This study, however, shows a non-pharmaceutical, noninvasive, and targeted electromagnetic (EM) technique to modulate ferroptosis—offering a potential pathway for THz-based therapies.
Why This Is Game-Changing
- Precision Intervention: THz radiation selectively decreases the ferric-ion-binding affinity on transferrin without needing systemic medications.
- Noninvasive Approach: Unlike conventional drugs or surgeries, terahertz exposure is externally applied and tunable.
- China Leads the Way: With ongoing studies across the non-ionizing electromagnetic spectrum, Chinese researchers are at the forefront of THz-based biomedical research and application.
Understanding the Science
What Is Ferroptosis?
- Ferroptosis is a programmed cell death mechanism heavily reliant on iron (Fe).
- Transferrin (Tf): A key transport protein in the bloodstream responsible for shuttling Fe³⁺ to cells.
- Fenton Reaction: Inside cells, Fe³⁺ converts to Fe²⁺ (and vice versa), which accelerates lipid peroxidation—a core hallmark of ferroptosis.
Because ferroptosis underlies many diseases (cancer, ischemic injury, neurodegeneration), controlling it has become a holy grail of new medical interventions.
Terahertz Waves (THz)
- THz Frequency Range: Sits between microwaves and infrared on the electromagnetic (EM) spectrum—around 0.1 THz to 10 THz or more.
- The Study’s Focus: A specific 8.7 μm (34.5 THz) wave can interfere with Fe³⁺–transferrin binding. The researchers discovered this both via molecular dynamics simulations (theory) and lab experiments (practice).
Non-Ionizing but Biologically Active
Unlike X-rays or gamma rays, THz waves are non-ionizing. However, this research shows that non-ionizing waves can still exert significant biological effects, especially by weakening certain molecular interactions without causing the direct DNA damage usually associated with ionizing radiation.
Key Findings at a Glance
- Molecular Dynamics Simulations
- Predicted that specific THz frequencies (8.7 μm / 34.5 THz) significantly decrease Fe³⁺–transferrin binding.
- Showed a strong wavelength dependency—small shifts in frequency matter.
- In Vitro Experiments
- Conducted in GF cells, HEK293T, and A549 cells.
- Confirmed that THz irradiation at 8.7 μm reduced iron uptake and lowered lipid peroxidation.
- Demonstrated a drop in Fe²⁺, malondialdehyde (MDA), and overall cell death markers associated with ferroptosis.
- In Vivo Evidence
- Tested an intestinal ischemia–reperfusion injury model—a classic scenario of ferroptosis.
- Found that targeted THz exposure nearly eliminated iron buildup, MDA generation, and lipid peroxidation in injured tissues.
- Validated the feasibility of THz-induced ferroptosis desensitization in living organisms.
Potential Biomedical Implications
1. A Novel Therapeutic Modality
Traditional ferroptosis-targeting drugs risk systemic side effects. By contrast, THz waves can be pointed (high directivity) at specific tissues or organs, potentially minimizing unwanted disruptions to iron homeostasis in the rest of the body.
2. Future Cancer Treatments
Many tumors rely on excess iron for rapid growth and often exhibit heightened ferroptosis sensitivity. Carefully calibrated THz treatment might stall iron influx to tumors, slowing proliferation or enhancing the efficacy of existing ferroptosis-inducing drugs.
3. Intestinal and Neurological Applications
- Ischemia–reperfusion injuries in gut tissues and the brain rely heavily on iron-driven oxidative damage.
- THz-based intervention might reduce post-injury complications or preserve neural function in stroke patients.
China’s Leadership in Non-Ionizing EMF Research
While terahertz technology is explored globally, Chinese institutions show robust advancement in RF, microwave, THz, and infrared research. This project exemplifies China’s push to harness non-ionizing EM for medical breakthroughs, offering safer, targeted therapies that do not rely on pharmaceuticals alone.
Technical Highlights
- Wavelength: 8.7 μm = 34.5 THz = 34,500 GHz
- Key Proteins: Transferrin, STEAP3, DMT1 (key iron-uptake regulators)
- Mechanism: Lowering Fe³⁺–Tf affinity disrupts the Fenton reaction chain, reducing lipid reactive oxygen species (ROS).
- Models Tested:
- In Vitro: GF, HEK293T, and A549 cell lines
- In Vivo: Intestinal ischemia–reperfusion injury in animal models
Frequently Asked Questions (FAQs)
1. Are Terahertz Waves Safe for Healthy Tissue?
This study indicates no major harm to normal cells under the tested THz conditions. However, comprehensive dosimetry and long-term safety studies must still be conducted before clinical adoption.
2. How Does THz Differ from 5G or Other RF Technologies?
- 5G typically ranges from millimeter waves (24–52 GHz) to lower frequencies.
- Terahertz goes beyond—100 GHz to several THz—offering distinct physical interaction with biological molecules.
3. Could This Replace Drug Therapies?
It’s too early to say. THz interventions might complement or enhance standard treatments. Because terahertz is noninvasive and targeted, it holds promise for precision medicine but will likely coexist with pharmacological approaches.
4. Is This Technology Clinically Available?
Currently, it’s preclinical research. The proof-of-concept is promising, but actual clinical devices that deliver focused THz at 34.5 THz for ferroptosis conditions remain in development.
5. Why Focus on Transferrin?
Transferrin is a central iron carrier in blood. Subtly tweaking its Fe³⁺ binding can modulate intracellular iron levels, especially in cells prone to ferroptosis. The challenge is not to induce overall iron deficiency, hence the appeal of a localized THz approach.
Conclusion
This terahertz wave research opens an exhilarating chapter in electromagnetic biomedical engineering—showing that non-ionizing radiation (at carefully chosen frequencies) might one day revolutionize how we treat diseases tied to ferroptosis. From cancer to intestinal ischemia, the potential to direct THz radiation and weaken Fe³⁺–transferrin binding offers a nonpharmaceutical strategy that could integrate seamlessly with other therapies.
As China and other nations continue advancing non-ionizing electromagnetic studies, we may see the emergence of electromagnetic “drugs” that harness THz frequencies for precise, minimal side-effect interventions. Whether it’s mitigating ferroptosis-driven damage or augmenting conventional treatments, THz is more than just a theoretical frontier—it might soon be part of mainstream medical toolkits.
Stay tuned for further updates, as the synergy of molecular dynamics simulations, in vitro assays, and in vivo validations continues to refine this technology. In the near future, doctors could use electromagnetic beams, not just pills or surgeries, to keep iron-dependent cell death in check.
Keywords & Subjects
- Subjects: Assays, Iron, Peroxidation, Quantum Mechanics, Radiation
- Keywords: terahertz wave, transferrin, ferroptosis, molecular dynamics simulation, lipid peroxidation, fenton reaction
References & Further Reading
- Li, X. et al. Terahertz Wave Desensitizes Ferroptosis by Inhibiting the Binding of Ferric Ions to Transferrin, ACS, 2025.
- Fan, C., et al. on terahertz biomedical research trends.
- Discussion on Fenton Reaction and lipid peroxidation from leading biochemistry sources.
