PMID- 36748266
OWN - NLM
STAT- MEDLINE
DCOM- 20230315
LR  - 20230315
IS  - 2047-4849 (Electronic)
IS  - 2047-4830 (Linking)
VI  - 11
IP  - 6
DP  - 2023 Mar 14
TI  - Mannose-mediated nanodelivery of methotrexate to macrophages augments rheumatoid 
      arthritis therapy.
PG  - 2211-2220
LID - 10.1039/d2bm02072f [doi]
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease that gravely 
      jeopardizes the quality of life of numerous people. Methotrexate (MTX) is a 
      disease-modifying anti-rheumatic drug commonly used in clinics; however, it 
      suffers from slow onset, moderate efficacy, and adverse reactions such as renal 
      dysfunction, myelosuppression, and bone erosion after long-term treatment. Here, 
      we explored macrophage targeted delivery of MTX using mannose-installed chimaeric 
      polymersomes (Man-PMTX) as an advanced treatment for RA. Man-PMTX exhibited high 
      ( approximately 18 wt%) and robust loading of MTX, uniform size of 51-55 nm, minimal hemolytic 
      activity, and glutathione-actuated drug release property. Man-PMTX showed better 
      uptake by activated macrophages than PMTX, and more repolarization of bone 
      marrow-derived macrophages (BMDMs) to anti-inflammatory M2 type macrophages and 
      less secretion of TNF-alpha and IL-1beta compared with free MTX and PMTX. In vivo 
      studies revealed that Man-PMTX showed significantly higher accumulation in 
      inflammatory joints than in healthy joints and effectively treated RA by 
      relieving inflammation, repolarizing macrophages from M1 type to M2 type, and 
      mitigating proinflammatory cytokines. Accordingly, Man-PMTX effectively protected 
      the synovium and bone from damage. Mannose-mediated nanodelivery of methotrexate 
      to macrophages appears to be an attractive strategy to augment rheumatoid 
      arthritis therapy.
FAU - Yang, Liang
AU  - Yang L
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, P. R. 
      China.
FAU - Sha, Yongjie
AU  - Sha Y
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, P. R. 
      China.
FAU - Wei, Yuansong
AU  - Wei Y
AD  - Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory 
      for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center 
      of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China. 
      lcyin@suda.edu.cn.
FAU - Fang, Hanghang
AU  - Fang H
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
FAU - Jiang, Jingjing
AU  - Jiang J
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
FAU - Yin, Lichen
AU  - Yin L
AUID- ORCID: 0000-0002-4573-0555
AD  - Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory 
      for Carbon-Based Functional Materials & Devices, Collaborative Innovation Center 
      of Suzhou Nano Science & Technology, Soochow University, Suzhou 215123, China. 
      lcyin@suda.edu.cn.
FAU - Zhong, Zhiyuan
AU  - Zhong Z
AUID- ORCID: 0000-0003-4175-4741
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
AD  - College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, P. R. 
      China.
FAU - Meng, Fenghua
AU  - Meng F
AUID- ORCID: 0000-0002-8608-7738
AD  - Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and 
      Materials Science, and State Key Laboratory of Radiation Medicine and Protection, 
      Soochow University, Suzhou, 215123, P. R. China. zyzhong@suda.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230314
PL  - England
TA  - Biomater Sci
JT  - Biomaterials science
JID - 101593571
RN  - YL5FZ2Y5U1 (Methotrexate)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Humans
MH  - *Methotrexate/pharmacology
MH  - Mannose/pharmacology
MH  - Quality of Life
MH  - *Arthritis, Rheumatoid/drug therapy
MH  - Macrophages
EDAT- 2023/02/08 06:00
MHDA- 2023/03/16 06:00
CRDT- 2023/02/07 03:42
PHST- 2023/02/08 06:00 [pubmed]
PHST- 2023/03/16 06:00 [medline]
PHST- 2023/02/07 03:42 [entrez]
AID - 10.1039/d2bm02072f [doi]
PST - epublish
SO  - Biomater Sci. 2023 Mar 14;11(6):2211-2220. doi: 10.1039/d2bm02072f.