PMID- 35807998
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2079-4991 (Print)
IS  - 2079-4991 (Electronic)
IS  - 2079-4991 (Linking)
VI  - 12
IP  - 13
DP  - 2022 Jun 23
TI  - Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis 
      and Nanoparticle Modification.
LID - 10.3390/nano12132161 [doi]
LID - 2161
AB  - Advances in drug delivery systems (DDSs) have enabled the specific delivery of 
      drugs to target cells. Subtilase cytotoxin (SubAB) produced by certain 
      enterohemorrhagic Escherichia coli strains induces endoplasmic reticulum (ER) 
      stress and suppresses nitric oxide generation in macrophages. We previously 
      reported that modification of SubAB with poly(D,L-lactide-co-glycolic) acid 
      (PLGA) nanoparticles (SubAB-PLGA NPs) increased intracellular uptake of SubAB and 
      had an anti-inflammatory effect on macrophages. However, specific delivery of 
      SubAB to macrophages could not be achieved because its effects on other cell 
      types were not negligible. Therefore, to suppress non-specific SubAB binding, we 
      used low-binding mutant SubAB(S35A) (S35A) in which the 35th serine of the B 
      subunit was mutated to alanine. In a macrophage cell line, PLGA NPs modified with 
      S35A (S35A-PLGA NPs) induced ER stress and had anti-inflammatory effects similar 
      to WT-PLGA NPs. However, in an epithelial cell line, S35A-PLGA NPs induced lower 
      ER stress than WT-PLGA NPs. These results suggest that S35A is selectively 
      delivered to macrophages rather than epithelial cells by modification with PLGA 
      NPs and exerts anti-inflammatory effects. Our findings provide a useful technique 
      for protein delivery to macrophages and encourage medical applications of DDSs 
      for the treatment of inflammatory diseases.
FAU - Harada, Ayaka
AU  - Harada A
AD  - Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, 
      Chuo-ku, Kumamoto 860-8555, Japan.
FAU - Tsutsuki, Hiroyasu
AU  - Tsutsuki H
AUID- ORCID: 0000-0002-6258-6313
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Zhang, Tianli
AU  - Zhang T
AUID- ORCID: 0000-0002-0543-4006
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Yahiro, Kinnosuke
AU  - Yahiro K
AD  - Department of Microbiology and Infection Control Sciences, Kyoto Pharmaceutical 
      University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan.
FAU - Sawa, Tomohiro
AU  - Sawa T
AD  - Department of Microbiology, Graduate School of Medical Sciences, Kumamoto 
      University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
FAU - Niidome, Takuro
AU  - Niidome T
AUID- ORCID: 0000-0002-8070-8708
AD  - Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, 
      Chuo-ku, Kumamoto 860-8555, Japan.
LA  - eng
GR  - 20K08823/Ministry of Education, Culture, Sports, Science and Technology/
GR  - 21H02071/Ministry of Education, Culture, Sports, Science and Technology/
GR  - JPMJCR18H5/Japan Science and Technology Agency/
GR  - 000/Takeda Science Foundation/
PT  - Journal Article
DEP - 20220623
PL  - Switzerland
TA  - Nanomaterials (Basel)
JT  - Nanomaterials (Basel, Switzerland)
JID - 101610216
PMC - PMC9268525
OTO - NOTNLM
OT  - PLGA nanoparticles
OT  - anti-inflammatory
OT  - controlled drug delivery
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/10 06:01
PMCR- 2022/06/23
CRDT- 2022/07/09 01:22
PHST- 2022/05/19 00:00 [received]
PHST- 2022/06/20 00:00 [revised]
PHST- 2022/06/20 00:00 [accepted]
PHST- 2022/07/09 01:22 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/10 06:01 [medline]
PHST- 2022/06/23 00:00 [pmc-release]
AID - nano12132161 [pii]
AID - nanomaterials-12-02161 [pii]
AID - 10.3390/nano12132161 [doi]
PST - epublish
SO  - Nanomaterials (Basel). 2022 Jun 23;12(13):2161. doi: 10.3390/nano12132161.