2025 · Chen — A Sustained H₂/Fluorouracil-Releasing Suppository for High-efficacy and Low-Toxicity Hydrogenochemotherapy of Colon Cancer.
Super-Abstract
Combining hydrogen gas with the standard chemotherapy drug 5-fluorouracil in a rectal suppository achieved complete tumour eradication in a mouse colon-cancer model — while simultaneously protecting the intestinal tissue from chemotherapy-induced damage. The hydrogen, released from cerium silicide nanoparticles in the suppository, scavenged excess reactive oxygen species in healthy cells and helped cancer cells undergo apoptosis via a separate pathway. (Advanced Healthcare Materials, 2025.)
Commentary
This is a preclinical animal study. The strategy of combining H₂ with 5-fluorouracil (5-FU) in a single suppository formulation exploits H₂'s dual role: it protects normal intestinal cells from oxidative damage caused by 5-FU, while at the same time enhancing the pro-apoptotic effect on tumour cells via a CO signalling pathway. Cerium silicide nanoparticles (CSN) provide sustained, synchronised release of both agents. The three-week daily treatment achieved complete tumour eradication without recurrence in the animal model — a striking result. However, all data are from a single mouse colon-cancer model, and the long-term safety profile of CSN nanoparticles and CO co-release has not yet been established in humans.
Key quotes
- „H2 generated by CSN reduces the toxicity of 5-FU to normal cells in the intestinal tract by scavenging over-expressed reactive oxygen species and correcting energy metabolism.“ — how H₂ protects healthy intestinal cells from chemotherapy damage
- „H2 also assists 5-FU to promote the apoptosis of colon tumor cells by inhibiting their respiration through a CO signaling pathway.“ — how H₂ enhances anti-tumour efficacy — via CO signalling
- „The 3-week treatment with the suppository once a day can not only completely eradicate colon tumors without tumor recurrence after suppository administration withdrawal, but also efficiently protect the intestinal tract from chemotherapeutic damage.“ — key outcome in the animal model
Our assessment
This is a preclinical animal study — results from a mouse colon-cancer model cannot be directly transferred to humans. The dual-action design (protecting normal tissue + enhancing tumour kill) is scientifically elegant and addresses a real clinical problem of chemotherapy intestinal toxicity. The CO co-release adds another mechanistic layer that requires independent safety characterisation. No human data exist; clinical translation requires extensive safety and pharmacokinetic studies. The result of complete tumour eradication, while striking, should be interpreted cautiously as it applies to one mouse tumour model only.
Study design
- Type: preclinical animal study · Model: mouse colon cancer (subcutaneous + orthotopic) · H₂ delivery: cerium silicide nanoparticles (CSN) in suppository — hydrolytic H₂ release synchronised with 5-FU
- Treatment: 5-FU/CSN@FAG suppository once daily for 3 weeks · Endpoints: tumour size/recurrence, intestinal histology, ROS levels, apoptosis markers, energy metabolism · Result: complete tumour eradication without recurrence; significant intestinal protection vs. 5-FU alone
Abstract
To attenuate the intestinal toxicity of chemotherapeutic drugs from rectal suppositories and enhance their chemotherapeutic outcome is greatly significant, but maintains a challenge. In this work, a new strategy of local synergistic hydrogenochemotherapy is proposed to attenuate side effects and enhance therapeutic efficacy based on the anti-cancer selectivity and normal cells-protecting effect of H2, and construct a novel anti-cancer formulation of rectal suppository (5-FU/CSN@FAG) by fatty acid glycerides (FAG) encapsulating 5-fluorouracil (5-FU, a first-line drug for colorectal cancer treatment) and cerium silicide nanoparticles (CSN) with a sustained hydrolytic H2 release behavior which is synchronous with 5-FU release. The 3-week treatment with the suppository once a day can not only completely eradicate colon tumors without tumor recurrence after suppository administration withdrawal, but also efficiently protect the intestinal tract from chemotherapeutic damage. Mechanistically, H2 generated by CSN reduces the toxicity of 5-FU to normal cells in the intestinal tract by scavenging over-expressed reactive oxygen species and correcting energy metabolism, and also assists 5-FU to promote the apoptosis of colon tumor cells by inhibiting their respiration through a CO signaling pathway. High biosafety and therapeutic validity endow the developed suppository with a high potential for clinical translation.
Source & links
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