@article{Wang2026, 
author = {Yueheng Wang and Changqing Yan and Lei Lei and Chenxin Ye and Hua Zhang and Xueqing Wang and Wenbing Dai and Shuguo Zheng and Qiang Zhang and Xiangyu Sun and Zhicheng Yan and Bing He},
title = {Manganese zoledronate sublingual nano-vaccine potentiates tumor inhibition and oral micro-ecology rebalance through mucosal and trained immunity},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {8},
pages = {94908788},
keywords = {trained immunity, mucosal immunity, sublingual nano-vaccine, nano-bisphosphonates, oral micro-ecology},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908788},
doi = {10.26599/NR.2026.94908788},
abstract = {The oral mucosa is a potent yet challenging site for vaccination, where physiological barriers and a tolerogenic immune microenvironment often limit effective immune response. However, existing delivery systems struggle to overcome these obstacles. Herein, we developed an oral mucosal nano-vaccine (MnZ-NV) via Mn2+-zoledronate coordination to co-encapsulate the Toll-like receptor 4 (TLR4) agonist Kdo2-lipid A (KLA) and antigen ovalbumin (OVA) within sub-50 nm particles. Upon sublingual administration, MnZ-NV demonstrated augmented mucosal penetration, lymph node targeting and dendritic cell activation, stimulating robust local and systemic cellular/humoral immunity. Furthermore, it induced trained immunity through splenic monocyte activation and bone marrow progenitor reprogramming, eliciting significant therapeutic and prophylactic efficacy against in-situ oral carcinoma, lung-metastatic melanoma, and pathogenic oral dysbiosis. This work provides a promising strategy that synergistically integrates innate, adaptive, and trained immunity for advanced mucosal immunotherapy.}
}