PMID- 36156794
OWN - NLM
STAT- MEDLINE
DCOM- 20230106
LR  - 20230210
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 180
IP  - 3
DP  - 2023 Feb
TI  - Targeted delivery of triptolide by dendritic cell-derived exosomes for colitis 
      and rheumatoid arthritis therapy in murine models.
PG  - 330-346
LID - 10.1111/bph.15958 [doi]
AB  - BACKGROUND AND PURPOSE: Triptolide (TP) elicits a beneficial effect in the 
      treatment of autoimmune diseases, such as ulcerative colitis (UC) and rheumatoid 
      arthritis (RA). However, its multiorgan toxicity needs to be resolved. Dendritic 
      cells (DCs) are the primary target of TP, which induces immunosuppression, and 
      DC-derived exosomes (DEX) can selectively enter DCs in vivo. Here, we 
      encapsulated TP with DEX (DEXTP) to generate TP-targeted delivery to reduce 
      toxicity. EXPERIMENTAL APPROACH: The effect of DEXTP was evaluated in murine 
      colitis and RA models. Toxicity was examined by haematoxylin and eosin staining 
      and serum biochemical marker detection. Affinity of DEXs for DCs was tracked by 
      fluorescent labelling. The immune environment was evaluated and mimicked in vitro 
      for further analysis of the mechanism. KEY RESULTS: DEXTP effectively carried TP 
      to DCs in vivo, and alleviated local inflammation and damage in colitis and RA 
      mice with no obvious toxicity. Additionally, DEXTP reshaped the immune milieu by 
      decreasing CD4(+) T-cell levels and increasing regulatory T-cell levels in vivo. 
      Furthermore, consistent T-cell differentiation was observed in vitro, and DC 
      activation was inhibited by alterations in surface factors and secrete cytokines, 
      and by induction of apoptosis or other form of death. CONCLUSIONS AND 
      IMPLICATIONS: Encapsulating TP with DEX is a new method that both reduces the 
      toxicity of TP and induces immunosuppression in UC and RA mice. The underlying 
      immune mechanism involves DEXTP targeting DCs in vivo, to inhibit DC activation 
      and induce DC apoptosis, which further induces T-cell immunosuppression.
CI  - (c) 2022 British Pharmacological Society.
FAU - Rao, Quan
AU  - Rao Q
AD  - Department of General Surgery, Beijing Friendship Hospital, Capital Medical 
      University, Beijing, China.
FAU - Ma, Guangchao
AU  - Ma G
AD  - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Li, Meng
AU  - Li M
AD  - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wu, Hao
AU  - Wu H
AD  - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Zhang, Yixi
AU  - Zhang Y
AD  - Department of General Surgery, Beijing Friendship Hospital, Capital Medical 
      University, Beijing, China.
FAU - Zhang, Congen
AU  - Zhang C
AD  - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Ma, Zhijie
AU  - Ma Z
AUID- ORCID: 0000-0001-7063-2474
AD  - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Huang, Luqi
AU  - Huang L
AD  - Resource Center for Chinese Materia Medica, China Academy of Chinese Medical 
      Sciences, Beijing, China.
LA  - eng
GR  - QML20200104/Beijing Municipal Administration of Hospitals' Youth Programme/
GR  - 81800577/National Natural Science Foundation of China/
GR  - 82004038/National Natural Science Foundation of China/
GR  - 7202033/Beijing Natural Science Foundation/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221025
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 19ALD1S53J (triptolide)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Disease Models, Animal
MH  - *Exosomes
MH  - *Arthritis, Rheumatoid/drug therapy
MH  - *Colitis/chemically induced/drug therapy
MH  - Dendritic Cells
OTO - NOTNLM
OT  - dendritic cell
OT  - encapsulation
OT  - exosome
OT  - rheumatoid arthritis
OT  - target delivery
OT  - tolerogenic
OT  - toxicity
OT  - triptolide
OT  - ulcerative colitis
EDAT- 2022/09/27 06:00
MHDA- 2023/01/07 06:00
CRDT- 2022/09/26 16:52
PHST- 2022/07/02 00:00 [revised]
PHST- 2022/02/09 00:00 [received]
PHST- 2022/09/09 00:00 [accepted]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2023/01/07 06:00 [medline]
PHST- 2022/09/26 16:52 [entrez]
AID - 10.1111/bph.15958 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2023 Feb;180(3):330-346. doi: 10.1111/bph.15958. Epub 2022 Oct 
      25.