Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Purification of His-Tagged Toxins
2.3. Site-Directed Mutagenesis of B Subunit of SubAB
2.4. HiLyte Fluor™ 555 (HF555) Labeling of Toxins
2.5. Cell Culture
2.6. Fluorescence Microscopy
2.7. Preparation of PLGA NPs
2.8. Preparation of FITC-Conjugated Oleylamine
2.9. Preparation of FITC-Labeled PLGA NPs
2.10. Characterization of PLGA NPs
2.11. Surface Modification of PLGA NPs with SubAB Toxins
2.12. Evaluation of pH-Dependent Release of His-Tagged SubAB Toxins
2.13. Intracellular Uptake of SubAB Toxin-PLGA NPs
2.14. Western Blotting
2.15. MTT Assay
2.16. Griess Assay
2.17. Statistical Analysis
3. Results and Discussion
3.1. Cell Recognition-Inactivated SubABS35A (S35A) Mutant Had Decreased Uptake by Cells
3.2. Preparation and Characterization of PLGA NPs Modified with Various SubAB Toxins
3.3. WT- and S35A-PLGA NPs Induce ER Stress and Inhibit iNOS Expression in Macrophages
3.4. S35A-PLGA NPs Do Not Induce ER Stress or Cytotoxicity in HeLa Cells
3.5. S35A-PLGA NPs Specifically Enter Macrophages, but Not Epithelial Cells
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Size (nm) | Polydispersity Index | Zeta Potential (mV) | |
---|---|---|---|
PLGA NPs | 260.7 ± 14.7 | 0.215 ± 0.012 | −32.8 ± 0.32 |
WT-PLGA NPs | 303.4 ± 4.9 | 0.367 ± 0.030 | 7.09 ± 1.32 |
A-PLGA NPs | 302.5 ± 5.6 | 0.355 ±0.008 | 8.89 ± 0.73 |
S35A-PLGA NPs | 302.7 ± 2.3 | 0.362 ±0.035 | 3.19 ± 0.15 |
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Harada, A.; Tsutsuki, H.; Zhang, T.; Yahiro, K.; Sawa, T.; Niidome, T. Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification. Nanomaterials 2022, 12, 2161. https://doi.org/10.3390/nano12132161
Harada A, Tsutsuki H, Zhang T, Yahiro K, Sawa T, Niidome T. Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification. Nanomaterials. 2022; 12(13):2161. https://doi.org/10.3390/nano12132161
Chicago/Turabian StyleHarada, Ayaka, Hiroyasu Tsutsuki, Tianli Zhang, Kinnosuke Yahiro, Tomohiro Sawa, and Takuro Niidome. 2022. "Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification" Nanomaterials 12, no. 13: 2161. https://doi.org/10.3390/nano12132161