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Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
by
Harada, Ayaka
, Tsutsuki, Hiroyasu
, Yahiro, Kinnosuke
, Zhang, Tianli
, Sawa, Tomohiro
, Niidome, Takuro
in
Acids
/ Alanine
/ anti-inflammatory
/ Binding
/ Cancer
/ Cell adhesion & migration
/ Chromatography
/ controlled drug delivery
/ Cytotoxicity
/ Drug delivery
/ Drug delivery systems
/ E coli
/ Endoplasmic reticulum
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Gene expression
/ Inflammation
/ Inflammatory diseases
/ Kinases
/ Macrophages
/ Medical research
/ Microscopy
/ Monoclonal antibodies
/ Mutagenesis
/ Nanoparticles
/ Nitric oxide
/ PLGA nanoparticles
/ Polylactide-co-glycolide
/ Proteins
/ Solvents
/ Subtilase
/ Toxins
2022
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Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
by
Harada, Ayaka
, Tsutsuki, Hiroyasu
, Yahiro, Kinnosuke
, Zhang, Tianli
, Sawa, Tomohiro
, Niidome, Takuro
in
Acids
/ Alanine
/ anti-inflammatory
/ Binding
/ Cancer
/ Cell adhesion & migration
/ Chromatography
/ controlled drug delivery
/ Cytotoxicity
/ Drug delivery
/ Drug delivery systems
/ E coli
/ Endoplasmic reticulum
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Gene expression
/ Inflammation
/ Inflammatory diseases
/ Kinases
/ Macrophages
/ Medical research
/ Microscopy
/ Monoclonal antibodies
/ Mutagenesis
/ Nanoparticles
/ Nitric oxide
/ PLGA nanoparticles
/ Polylactide-co-glycolide
/ Proteins
/ Solvents
/ Subtilase
/ Toxins
2022
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Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
by
Harada, Ayaka
, Tsutsuki, Hiroyasu
, Yahiro, Kinnosuke
, Zhang, Tianli
, Sawa, Tomohiro
, Niidome, Takuro
in
Acids
/ Alanine
/ anti-inflammatory
/ Binding
/ Cancer
/ Cell adhesion & migration
/ Chromatography
/ controlled drug delivery
/ Cytotoxicity
/ Drug delivery
/ Drug delivery systems
/ E coli
/ Endoplasmic reticulum
/ Enzymes
/ Epithelial cells
/ Epithelium
/ Gene expression
/ Inflammation
/ Inflammatory diseases
/ Kinases
/ Macrophages
/ Medical research
/ Microscopy
/ Monoclonal antibodies
/ Mutagenesis
/ Nanoparticles
/ Nitric oxide
/ PLGA nanoparticles
/ Polylactide-co-glycolide
/ Proteins
/ Solvents
/ Subtilase
/ Toxins
2022
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Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
Journal Article
Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
2022
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Overview
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 SubABS35A (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.
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