Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study

Radiation-induced oral mucositis (RIOM) is the most common oral complication faced by patients with head and neck cancer undergoing radiotherapy or chemotherapy, significantly diminishing their quality of life. While previous studies have investigated single K12 probiotics for RIOM, they often lacke...

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Main Authors: ZhiHui Li, Dan He, Ye Zhang, Zhou Shi, Quanjin Tang, Zixia Li, Xingchen Peng, Dong Li, Daijun Zhou
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425007124
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author ZhiHui Li
Dan He
Ye Zhang
Zhou Shi
Quanjin Tang
Zixia Li
Xingchen Peng
Dong Li
Daijun Zhou
author_facet ZhiHui Li
Dan He
Ye Zhang
Zhou Shi
Quanjin Tang
Zixia Li
Xingchen Peng
Dong Li
Daijun Zhou
author_sort ZhiHui Li
collection DOAJ
description Radiation-induced oral mucositis (RIOM) is the most common oral complication faced by patients with head and neck cancer undergoing radiotherapy or chemotherapy, significantly diminishing their quality of life. While previous studies have investigated single K12 probiotics for RIOM, they often lacked stability, free radical scavenging activity, and precise oral targeting. To overcome these challenges, we developed K12@Lip@GSH, an innovative oral probiotic that encapsulates K12 within liposomes to enhance stability and scavenging efficacy, while utilizing a glutathione (GSH) transporter-mediated targeting mechanism that exploits the favorable the overexpression of GSH transporters in RIOM. Evaluations conducted in RIOM mouse models subjects demonstrated favorable outcomes, including a reduction in ulcer size, increased epithelial cellularity and mucosal thickness, enhanced epithelial proliferation, and decreased apoptosis. Genomic analysis further indicated improvements in mRNA pathways associated with the recovery from RIOM. Additionally, K12@Lip@GSH was shown to restore the balance of oral microbiota and reduce the abundance of oral anaerobes in RIOM mice. Subsequently, the safety and efficacy of K12@Lip@GSH were confirmed through further single-arm, single-center prospective clinical trials. The clinical trial data demonstrated a manageable safety profile in the cohort of 22 enrolled patients. Treatment-related adverse events (TRAEs) were infrequent, occurring in only 4.5 % of participants, with reported symptoms including flatulence and dyspepsia. Although 59.1 % of patients experienced oral mucositis (OM), the incidence of severe OM (grade 4) was 0.0 %, and no interruptions in radiotherapy treatment occurred due to OM. Overall, K12@Lip@GSH shows promise as an adjuvant strategy for improving radiation-induced oral mucositis (RIOM) in cancer patients undergoing radiotherapy.
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spelling doaj-art-d28a052d0c574d8882f69c2edeaad8db2025-08-20T02:47:28ZengElsevierMaterials Today Bio2590-00642025-10-013410214210.1016/j.mtbio.2025.102142Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical studyZhiHui Li0Dan He1Ye Zhang2Zhou Shi3Quanjin Tang4Zixia Li5Xingchen Peng6Dong Li7Daijun Zhou8Department of Oncology, General Hospital of Western Theater Command, Chengdu, 610083, China; Department of Oncology, Dazhu County People's Hospital, Sichuan Province, Dazhou, 635100, ChinaDepartment of Oncology, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, ChinaDepartment of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, ChinaDepartment of Oncology, Dazhu County People's Hospital, Sichuan Province, Dazhou, 635100, ChinaDepartment of Oncology, Dazhu County People's Hospital, Sichuan Province, Dazhou, 635100, ChinaDepartment of Biotherapy, Cancer Center, West China Hospital & State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center, West China Hospital & State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, ChinaDepartment of Oncology, General Hospital of Western Theater Command, Chengdu, 610083, ChinaDepartment of Oncology, General Hospital of Western Theater Command, Chengdu, 610083, China; Corresponding author. The General Hospital of Western Theater Command, No. 270, Rongdu Avenue, Jinniu District, Chengdu, Sichuan Province, 610083, China.Radiation-induced oral mucositis (RIOM) is the most common oral complication faced by patients with head and neck cancer undergoing radiotherapy or chemotherapy, significantly diminishing their quality of life. While previous studies have investigated single K12 probiotics for RIOM, they often lacked stability, free radical scavenging activity, and precise oral targeting. To overcome these challenges, we developed K12@Lip@GSH, an innovative oral probiotic that encapsulates K12 within liposomes to enhance stability and scavenging efficacy, while utilizing a glutathione (GSH) transporter-mediated targeting mechanism that exploits the favorable the overexpression of GSH transporters in RIOM. Evaluations conducted in RIOM mouse models subjects demonstrated favorable outcomes, including a reduction in ulcer size, increased epithelial cellularity and mucosal thickness, enhanced epithelial proliferation, and decreased apoptosis. Genomic analysis further indicated improvements in mRNA pathways associated with the recovery from RIOM. Additionally, K12@Lip@GSH was shown to restore the balance of oral microbiota and reduce the abundance of oral anaerobes in RIOM mice. Subsequently, the safety and efficacy of K12@Lip@GSH were confirmed through further single-arm, single-center prospective clinical trials. The clinical trial data demonstrated a manageable safety profile in the cohort of 22 enrolled patients. Treatment-related adverse events (TRAEs) were infrequent, occurring in only 4.5 % of participants, with reported symptoms including flatulence and dyspepsia. Although 59.1 % of patients experienced oral mucositis (OM), the incidence of severe OM (grade 4) was 0.0 %, and no interruptions in radiotherapy treatment occurred due to OM. Overall, K12@Lip@GSH shows promise as an adjuvant strategy for improving radiation-induced oral mucositis (RIOM) in cancer patients undergoing radiotherapy.http://www.sciencedirect.com/science/article/pii/S2590006425007124Oral mucositisProbioticHead and neck cancerK12
spellingShingle ZhiHui Li
Dan He
Ye Zhang
Zhou Shi
Quanjin Tang
Zixia Li
Xingchen Peng
Dong Li
Daijun Zhou
Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
Materials Today Bio
Oral mucositis
Probiotic
Head and neck cancer
K12
title Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
title_full Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
title_fullStr Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
title_full_unstemmed Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
title_short Targeted prevention of radiation-induced oral mucositis by glutathione-modified liposome coated K12 probiotics and clinical study
title_sort targeted prevention of radiation induced oral mucositis by glutathione modified liposome coated k12 probiotics and clinical study
topic Oral mucositis
Probiotic
Head and neck cancer
K12
url http://www.sciencedirect.com/science/article/pii/S2590006425007124
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