2. Academic Validation
  3. Coassembly Nanomedicine Mediated by Intermolecular Interactions Between Methotrexate and Baricitinib for Improved Rheumatoid Arthritis Treatment

Coassembly Nanomedicine Mediated by Intermolecular Interactions Between Methotrexate and Baricitinib for Improved Rheumatoid Arthritis Treatment

  • ACS Nano. 2024 Mar 4. doi: 10.1021/acsnano.3c12692.
Hehe Xiong 1,  Heng Zhang 1,  Yatong Qin 1,  Jinmin Ye 1,  Fantian Zeng 1,  Peng Xie 1,  Changrong Shi 1,  Changyuan Luo 1,  Weizhuo Xu 1,  Chunyang Yu 2 3,  Zijian Zhou 1,  Xiaoyuan Chen 4 5 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
  • 2 School of Chemistry & Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 3 Key Laboratory of Green and High-end Utilization of Salt Lake Resources, Chinese Academy of Sciences, Xining 810008, China.
  • 4 Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore.
  • 5 Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
  • 6 Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
  • 7 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Biopolis Drive, Proteos, Singapore 138673, Singapore.
PMID: 38437640 DOI: 10.1021/acsnano.3c12692
Abstract

The combination of anti-rheumatoid arthritis (RA) drugs methotrexate (MTX) and baricitinib (BTN) has been reported to improve RA treatment efficacy. However, study on the strategy of combination is elusive when considering the benefit of the synergy between MTX and BTN. In this study, we found that the N-heterocyclic rings in the MTX and BTN offer hydrogen bonds and π-π stacking interactions, driving the formation of exquisite vesicular morphology of nanovesicles, denoted as MB NVs. The MB NVs with the MTX/BTN weight ratio of 2:1, MB NVs (2:1), showed an improved anti-RA effect through the synergy between the anti-inflammatory and antiproliferative responses. This work presents that the intermolecular interactions between drug molecules could mediate the coassembly behavior into nanomedicine as well as the therapy synergy both in vitro and in vivo, which may provide further understanding on the rational design of combination nanomedicine for therapeutic purposes.

Keywords

coassembly; drug combination; intermolecular interaction; nanodrug delivery; nanovesicles.

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