Theranostics 2021; 11(8):3694-3709. doi:10.7150/thno.52891
Polysaccharide mycophenolate-based nanoparticles for enhanced immunosuppression and treatment of immune-mediated inflammatory diseases
1. Key Laboratory of Material Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
2. Department of Dermatology, Union Hospital, Tongji Medical College, HUST, Wuhan 430022, China.
* These authors contributed equally to this study.
Li Y, Lou Y, Chen Y, Yang J, Li D, Jiang B, Lan J, Wen J, Fu Y, Zhang Y, Tao J, Zhu J. Polysaccharide mycophenolate-based nanoparticles for enhanced immunosuppression and treatment of immune-mediated inflammatory diseases. Theranostics 2021; 11(8):3694-3709. doi:10.7150/thno.52891. Available from https://www.thno.org/v11p3694.htm
Immune-mediated inflammatory diseases (IMIDs) are characterized by immune dysregulation and severe inflammation caused by the aberrant and overactive host immunological response. Mycophenolic acid (MPA)-based immunosuppressive drugs are potential treatments for IMIDs because of their mild side-effect profile; however, their therapeutic effects are limited by the high albumin binding rate, unsatisfactory pharmacokinetics, and undefined cellular uptake selectivity.
Methods: Polysaccharide mycophenolate was synthesized by conjugating MPA molecules to dextran (a typical polysaccharide widely used in drug delivery) and encapsulated extra free MPA molecules to fabricate MPA@Dex-MPA nanoparticles (NPs). The efficacy of these NPs for mediating immunosuppression and treatment of IMIDs was evaluated in imiquimod-induced psoriasis-like skin inflammation in Balb/c mice, a representative IMID model.
Results: The MPA@Dex-MPA NPs exhibited high MPA loading efficiency, low albumin binding rates, and sustained MPA release, resulting in improved pharmacokinetics in vivo. Compared to free MPA, MPA@Dex-MPA NPs induced more robust therapeutic effects on IMIDs. Mechanistic studies indicated that MPA@Dex-MPA NPs were primarily distributed in dendritic cells (DCs) and significantly suppressed the overactivated DCs in vivo and in vitro. Furthermore, the recovered DCs rehabilitated the IL-23/Th17 axis function and significantly ameliorated imiquimod-induced psoriasis-like skin inflammation. Importantly, MPA@Dex-MPA NPs showed favorable safety and biocompatibility in vivo.
Conclusion: Our results indicated the polysaccharide mycophenolate-based NPs to be highly promising for IMID treatment.
Keywords: mycophenolate, polysaccharide, immunosuppression, psoriasis, immune-mediated inflammatory diseases