- 著者
- Ayaka Harada Hiroyasu Tsutsuki Tianli Zhang Ruda Lee Kinnosuke Yahiro Tomohiro Sawa Takuro Niidome
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.68, no.4, pp.363-368, 2020-04-01 (Released:2020-04-01)
- 参考文献数
- 39
- 被引用文献数
- 7
Poly(D,L-lactide-co-glycolic) acid (PLGA) is a synthetic copolymer that has been used to design micro/nanoparticles as a carrier for macromolecules, such as protein and nucleic acids, that can be internalized by the endocytosis pathway. However, it is difficult to control the intracellular delivery to target organelles. Here we report an intracellular delivery system of nanoparticles modified with bacterial cytotoxins to the endoplasmic reticulum (ER) and anti-inflammatory activity of the nanoparticles. Subtilase cytotoxin (SubAB) is a bacterial toxin in certain enterohemorrhagic Escherichia coli (EHEC) strains that cleaves the host ER chaperone BiP and suppresses nuclear factor-kappaB (NF-κB) activation and nitric oxide (NO) generation in macrophages at sub-lethal concentration. PLGA-nanoparticles were modified with oligo histidine-tagged (6 × His-tagged) recombinant SubAB (SubAB-PLGA) through a pH-sensitive linkage, and their translocation to the ER in macrophage cell line J774.1 cells, effects on inducible NO synthase (iNOS), and levels of tumor necrosis factor (TNF)-α cytokine induced by lipopolysaccharide (LPS) were examined. Compared with free SubAB, SubAB-PLGA was significantly effective in BiP cleavage and the induction of the ER stress marker C/EBP homologous protein (CHOP) in J774.1 cells. Furthermore, SubAB-PLGA attenuated LPS-stimulated induction of iNOS and TNF-α. Our findings provide useful information for protein delivery to macrophages and may encourage therapeutic applications of nanoparticles to the treatment of inflammatory diseases.
- 著者
- Masanori Fujii Naotoshi Nakashima Takuro Niidome Yasuro Niidome
- 出版者
- (社)日本化学会
- 雑誌
- Chemistry Letters (ISSN:03667022)
- 巻号頁・発行日
- vol.43, no.1, pp.131-133, 2014-01-05 (Released:2014-01-05)
- 参考文献数
- 23
- 被引用文献数
- 13
Laser-induced desorption and ionization (LDI) of gold ions (Aun+: n = 1–3) were observed from gold nanorods in a liver tissue section (thickness: 10 µm). Larger amounts of gold nanorods produced stronger mass signals. Organic molecules in the tissue were not detected and did not inhibit the LDI processes of the gold nanorods in the tissue. Because of the selective LDI processes of the gold nanorods, the distribution of gold in the liver was successfully determined by imaging mass spectrometry.