Synthesis of high functionality and quality mannose-grafted lipids to produce macrophage-targeted liposomes
| Autor: | Shigeru Kawakami, Tadaharu Suga, Yorinao Chinda, Tatsuo Inamine, Masayori Hagimori, Yuki Fuchigami, Naoya Kato, Kazuto Yamanami |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Macrophage Pharmaceutical Science Mannose Receptors Cell Surface 02 engineering and technology Serine?glycine repeat spacer 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Peptide synthesis Animals Lectins C-Type Receptor Solid-Phase Synthesis Techniques Mice Inbred ICR Liposome Tumor microenvironment Macrophages Lipid 021001 nanoscience & nanotechnology Lipids In vitro Mannose-Binding Lectins 030104 developmental biology chemistry Biochemistry Organ Specificity Liposomes Drug delivery 0210 nano-technology Mannose Receptor Mannose receptor |
| Zdroj: | European Journal of Pharmaceutical Sciences. 123:153-161 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2018.07.036 |
| Popis: | The mannose receptor, which is responsible for tumor invasion, proliferation, and metastasis in the tumor microenvironment, is overexpressed in tumor-associated macrophages. Mannose is commonly applied to PEGylated liposomes in macrophage-targeted cancer therapy. To develop a high functionality and quality (HFQ) lipid for macrophage-targeted liposomes, we designed a novel mannosylated lipid with improved mannose receptor binding affinity using serine?glycine repeats (SG)n. We synthesized Man(S)-(SG)5-SSK-K(Pal)2 using only a fluorenylmethyloxycarbonyl (Fmoc) protecting group solid-phase peptide synthesis method, which produced a high-quality lipid at a moderately good yield. We then prepared Man-(SG)5/PEGylated liposomes using a post-insertion technique to insert Man(S)-(SG)5-SSK-K(Pal)2 into the PEGylated liposomes. In vitro cell investigations revealed that the Man-(SG)5/PEGylated liposomes effectively associated with mouse peritoneal macrophages by interacting with the mannose receptors. The results suggest that we produced a novel high-quality, highly functional mannosylated lipid that is suitable for clinical drug delivery applications. European Journal of Pharmaceutical Sciences, 123, pp.153-161; 2018 |
| Databáze: | OpenAIRE |
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