A1 Refereed original research article in a scientific journal
Oral Dosed Organo-Silica Nanoparticles Restore Glucose Homeostasis and β-Cell Function in Diabetes Rats
Authors: Chu, Chenxiao; Wei, Mingli; Bian, Che; Bi, Xiaoshuang; Deng, Yaxin; Xiao, Peifu; Zhao, Jiansong; Wang, Yuying; He, Haibing; Gou, Jingxin; Yin, Tian; Tang, Xing; Yang, Li; Zhang, Hongbo; Zhang, Yu
Publisher: Wiley-VCH
Publication year: 2025
Journal: Advanced Functional Materials
Article number: e19628
ISSN: 1616-301X
eISSN: 1616-3028
DOI: https://doi.org/10.1002/adfm.202519628
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1002/adfm.202519628
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/506132393
Type 2 diabetes mellitus (T2DM) persists as a global health challenge, with current therapies inadequately addressing the intertwined pathologies of hyperglycemia, oxidative stress, and β-cell dysfunction. Here, an oral nanotherapeutic platform, MOP@T@D, engineered to restore glucose homeostasis and rejuvenate pancreatic β-cells is developed. The platform is constructed by co-loading insulin and glucose oxidase (GOx) into diselenide-bridged mesoporous organosilicon nanoparticles (MON), followed by sequential coating with transferrin (Tf) and functionalization with deoxycholic acid (Dc). MOP@T@D demonstrates efficient intestinal absorption and liver-targeted delivery, achieving an oral bioavailability of 10.6%. Under hyperglycemic conditions, GOx-generated H2O2 cleaves the diselenide bonds in the MON framework, resulting in rapid insulin release with 8.7-fold higher cumulative release compared to normoglycemic conditions. Simultaneously, the metabolized selenium derivatives progressively upregulate key selenoproteins, enhancing glutathione peroxidase (Gpx) activity by 31%, which effectively neutralizes oxidative stress and suppresses NF-κB-mediated inflammation. In a T2DM rat model, this therapy increases the islet area by 26.7% and restores insulin secretion to 74.6% of the physiological level. Notably, the system maintains normal blood glucose levels for two weeks after cessation of administration. In summary, through a simple oral dose, MOP@T@D not only stabilizes glycemic fluctuations but also addresses the root pathophysiology of T2DM.
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Funding information in the publication:
This work was supported by the National Natural Science Foundation of China (Grant Nos. U22A20384, 82204298, and 82172086), National Key R&D Program of China [2020YFE0201700], Frontier Technology Platform Program of Educational Department of Liaoning Province [LJ232410163022], and International Industry Technology Research and Development Program [2025JH2/101900046]. H. Z. acknowledged the Research Project (347897), Solution for Health Profile (336355), InFLAMES Flagship (337531), and “Printed Intelligence Infrastructure (PII-FIRI)” from Research Council of Finland. It was also part of the activities of the Åbo Akademi University Foundation (SÅA) funded Center of Excellence in Research “Materials-driven solutions for combating antimicrobial resistance (MADNESS)”.
Open access publishing facilitated by Abo Akademi, as part of the Wiley - FinELib agreement.
