Main Session
Sep 29
PQA 06 - Radiation and Cancer Biology, Health Care Access and Engagement

3178 - Molybdenum Oxide Nanoparticles Alleviates Radiation-Induced Enteritis by Restoring H2S Homeostasis

05:00pm - 06:00pm PT
Hall F
Screen: 20
POSTER

Presenter(s)

Jie Zhou, PhD, RT - Sichuan Cancer Hospital and Institute, Chengdu, Sichuan

J. Zhou1, C. Yang2, and P. Zhang1; 1Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, 2Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital &Institute,Sichuan Cancer Center ,School of Medicine,University of Electronic Science and Technology of China, Chengdu, China

Purpose/Objective(s):

Radiation-induced enteritis is the most common side effect during radiotherapy of abdominal or pelvic malignancies without satisfactory treatment. Emerging evidence highlights hydrogen sulfide (H2S) as a vital mediator for gut microbiota homeostasis and intestinal barrier protection. Irradiation accelerates the accumulation of H2S in the gut, however, whether and how dysregulation H2S interfere radiation-induced enteritis remains poorly understood. Here, we aimed to develop a novel endogenous H2S-responsive molybdenum oxide nanotherapeutics(MoOx)to restore H2S homeostasis after radiotherapy and mitigate intestinal radiation injury.

Materials/Methods:

MoOx was synthesized via H2O2-assisted ultrasonic exfoliation of Mo2C, characterized by TEM/XRD. Intestinal epithelial cells (IEC-6) exposed to 8 Gy X-ray irradiation were analyzed for H2S levels via WSP-5 probe, CBS and CSE activity was assessed by ELISA. In vivo efficacy was evaluated in C57BL/6 mice subjected to 7 Gy abdominal irradiation, with once oral administration of MoOx. We also conducted histopathological assessment by hematoxylin-eosin staining, gut microbiota profiling via fecal 16S ribosomal RNA sequencing, and survival monitoring.

Results:

We found that MoOx effectively alleviates the effects of irradiation on intestinal epithelial barrier, inflammation, and bacterial homeostasis, leading to an alleviated intestinal injury both in vitro and in vivo. Mechanistically, we revealed that MoOx restores H2S homeostasis through triple-pathway. Firstly, MoOx directly neutralizes luminal H2S, forming antioxidant polyoxometalates (Mo-POMs) that decreases radiation-induced reactive oxygen species (ROS) production and its DNA damage. Secondly, MoOx suppresses host-derived H2S synthesis by inhibiting pyridoxal phosphate (PLP1)-dependent CBS/CSE activity. Thirdly, MoOx remodels gut microbiota composition, selectively reducing sulfate-reducing bacteria (SRB) abundance and their H2S production.

Conclusion:

MoOx attenuate radiation enteritis by neutralizing luminal H2S into antioxidant Mo-POMs, blocking host H2S production via PLP1-dependent CBS/CSE inhibition, and suppressing microbial H2S generation. The multi-target strategy synergistically enhances intestinal barrier function, alleviate pro-inflammatory cascades, and promotes mucosal regeneration, may serve as a novel therapeutic paradigm for radiation-induced gastrointestinal injury.