Hydrogen Nanomicelles Heal Chemo-Induced Mouth Sores in Mice
- Authors
- Dongwei Chen, Shahab Uddin, Bozhao Wang, Hai Yao, Xueyan Que, Jian Li, Ling Xu
- Journal
- International Journal of Biological Macromolecules
- Year
- 2026
- DOI
- 10.1016/j.ijbiomac.2026.153863
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Chemotherapy-Induced Oral Mucositis
- Body System
- Oral/Gastrointestinal
TL;DR
A quercetin–hydrogen nanomicelle reduced oxidative stress and inflammation while improving oral mucosal repair in mice with chemotherapy-induced oral mucositis.
Key Finding
Mice with chemotherapy-induced oral mucositis treated with the hydrogen-quercetin nanoparticles showed nearly double the epithelial (mouth lining) thickness compared to untreated mice, along with significantly lower levels of inflammatory proteins TNF-α and IL-6.
Summary
This study tested a new nanoparticle (tiny engineered particle) delivery system that combined quercetin (a plant-based antioxidant) and molecular hydrogen to treat chemotherapy-induced oral mucositis — painful sores in the mouth caused by cancer treatment. Researchers built the particles using a material called carboxymethyl chitosan and tested them in mice given the chemotherapy drug 5-fluorouracil. The nanoparticles reduced inflammation, neutralized harmful molecules called free radicals, and helped the mouth's tissue lining heal compared to untreated mice.
Practical Takeaway
This is early-stage animal research and has not been tested in humans, so no conclusions can be drawn about benefits for people. The study suggests that combining molecular hydrogen with antioxidants in a specialized delivery system may support tissue healing and reduce inflammation in chemotherapy-related mouth sores, but clinical trials would be needed to know if this approach is safe or effective for cancer patients.
Abstract
Chemotherapy-induced oral mucositis (CIOM) is a debilitating adverse effect characterized by oxidative stress and inflammatory cascade-driven mucosal injury, yet current clinical interventions remain largely symptomatic and fail to address the underlying pathological mechanisms. This study aimed to develop a carboxymethyl chitosan (CMCTs)-based nanomicellar platform co-loaded with quercetin and molecular hydrogen to simultaneously target oxidative stress, inflammation, and mucosal repair in CIOM. Quercetin-CMCTs nano hydrogen-rich micelles (QCH-NMs) were prepared via ultrasound-assisted self-assembly and characterized by dynamic light scattering, zeta potential measurement, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. In vitro antioxidant capacity was assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical, and superoxide radical scavenging assays. Therapeutic efficacy and biosafety were evaluated in a 5-fluorouracil (5-FU)-induced murine CIOM model using histological staining, immunohistochemistry, enzyme-linked immunosorbent assay, and hemolysis testing. The optimized QCH-NMs exhibited a hydrodynamic diameter of 164.18 nm, polydispersity index of 0.03, and zeta potential of +30.2 mV, with sustained hydrogen retention of 1238 ppb at 12 h under physiological pH. Radical scavenging activity reached 88.0% (DPPH), 68.6% (hydroxyl), and 95.2% (superoxide). In vivo, QCH-NMs maintained 100% survival, restored epithelial thickness to 59.16 ± 2.97 μm versus 31.56 ± 2.48 μm in the model group, upregulated Ki67 (26.53%) and Nrf2 (23.41%) expression, significantly reduced serum tumour necrosis factor-α and interleukin-6 levels, and demonstrated excellent biocompatibility with a hemolysis rate of 0.9% and no detectable organ toxicity. These findings indicate that QCH-NMs represent a safe, multi-target adjunctive strategy for CIOM management with promising preclinical potential.