Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
Advances in drug delivery systems (DDSs) have enabled the specific delivery of drugs to target cells. Subtilase cytotoxin (SubAB) produced by certain enterohemorrhagic <i>Escherichia coli</i> strains induces endoplasmic reticulum (ER) stress and suppresses nitric oxide generation in macr...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/12/13/2161 |
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| author | Ayaka Harada Hiroyasu Tsutsuki Tianli Zhang Kinnosuke Yahiro Tomohiro Sawa Takuro Niidome |
| author_facet | Ayaka Harada Hiroyasu Tsutsuki Tianli Zhang Kinnosuke Yahiro Tomohiro Sawa Takuro Niidome |
| author_sort | Ayaka Harada |
| collection | DOAJ |
| description | Advances in drug delivery systems (DDSs) have enabled the specific delivery of drugs to target cells. Subtilase cytotoxin (SubAB) produced by certain enterohemorrhagic <i>Escherichia coli</i> 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<sub>S35A</sub> (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. |
| first_indexed | 2024-03-09T12:42:31Z |
| format | Article |
| id | doaj.art-15ba408034274fc29b5c8652a3aecdc9 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-09T12:42:31Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-15ba408034274fc29b5c8652a3aecdc92023-11-30T22:16:03ZengMDPI AGNanomaterials2079-49912022-06-011213216110.3390/nano12132161Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle ModificationAyaka Harada0Hiroyasu Tsutsuki1Tianli Zhang2Kinnosuke Yahiro3Tomohiro Sawa4Takuro Niidome5Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, JapanDepartment of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, JapanDepartment of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, JapanDepartment of Microbiology and Infection Control Sciences, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Microbiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, JapanFaculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, JapanAdvances in drug delivery systems (DDSs) have enabled the specific delivery of drugs to target cells. Subtilase cytotoxin (SubAB) produced by certain enterohemorrhagic <i>Escherichia coli</i> 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<sub>S35A</sub> (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.https://www.mdpi.com/2079-4991/12/13/2161PLGA nanoparticlesanti-inflammatorycontrolled drug delivery |
| spellingShingle | Ayaka Harada Hiroyasu Tsutsuki Tianli Zhang Kinnosuke Yahiro Tomohiro Sawa Takuro Niidome Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification Nanomaterials PLGA nanoparticles anti-inflammatory controlled drug delivery |
| title | Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification |
| title_full | Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification |
| title_fullStr | Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification |
| title_full_unstemmed | Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification |
| title_short | Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification |
| title_sort | controlled delivery of an anti inflammatory toxin to macrophages by mutagenesis and nanoparticle modification |
| topic | PLGA nanoparticles anti-inflammatory controlled drug delivery |
| url | https://www.mdpi.com/2079-4991/12/13/2161 |
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