Projects per year
Abstract
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.
| Original language | English |
|---|---|
| Journal | Advanced Functional Materials |
| DOIs | |
| Publication status | Accepted/In press - 2025 |
| MoE publication type | A1 Journal article-refereed |
Funding
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)”.
Keywords
- diselenide bonds
- glucose responsive release
- mesoporous organosilicon nanoparticles
- oral insulin
- β-cells protection
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Åbo Akademi Functional Printing Center
Toivakka, M. (PI), Rosenholm, J. (PI), Anttu, N. (PI), Bobacka, J. (PI), Huynh, T. P. (PI), Peltonen, J. (PI), Wang, X. (PI), Wilen, C.-E. (PI), Xu, C. (PI), Zhang, H. (PI) & Österbacka, R. (PI)
Faculty of Science and EngineeringFacility/equipment: Facility
Projects
- 1 Active
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MADNESS: Centre of Excellence in Materials-driven solutions for combatting antimicrobial resistance
Rosenholm, J. (Principal Investigator), Porres Paltor, I. (Co-Principal Investigator), Bansal, K. (Coordinator), Lafond, S. (Co-Principal Investigator), Uppstu, P. (Co-Principal Investigator), Viitala, T. (Co-Principal Investigator), Wang, X. (Co-Principal Investigator), Wilen, C.-E. (Co-Principal Investigator), Xu, C. (Co-Principal Investigator), Zhang, H. (Co-Principal Investigator), Lu, Z. (Co-Investigator), Verma, J. (Co-Investigator), Kumar, V. (Co-Investigator), Frejborg, F. (Co-Investigator), Wang, S. (Co-Investigator), Ran, M. (Co-Investigator), Ma, X. (Co-Investigator), Yang, W. (Co-Investigator), Liang, S. (Co-Investigator), Zhang, Y. (Co-Investigator), Fan, L. (Co-Investigator), Chen, Y. (Co-Investigator), Wang, L. (Co-Investigator), Zhuang, P. (Co-Investigator), Rajan Prakash, D. (Co-Investigator), Howaili, F. (Co-Investigator), Gulshan, R. (Co-Investigator), Yadav, D. (Co-Investigator), Pathak, C. (Co-Investigator), Mustafa, R. (Co-Investigator), Rostami, L. (Co-Investigator), Jafari Dargahlou, M. (Co-Investigator), Nygård, A. (Co-Investigator) & Manasut, P. (Co-Investigator)
01/01/24 → 31/12/28
Project: Foundation