Using a membrane-penetrating-peptide to anchor ligands in the liposome membrane facilitates targeted drug delivery
Antimicrobial peptides (AMPs) are typical cell penetrating peptides (CPPs) that intercalate into biomembranes and exhibit broad activities. We designed a triple fusion protein consisting of an AMP, Ib-AMP4 at the N-terminus, a fluorescent GFP probe in the center, and the tumor-targeting peptide P1c...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2020
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| In: |
Bioconjugate chemistry
Year: 2019, Volume: 31, Issue: 1, Pages: 113-122 |
| ISSN: | 1520-4812 |
| DOI: | 10.1021/acs.bioconjchem.9b00798 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acs.bioconjchem.9b00798
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| Author Notes: | Xiaobo Fan, Hongbo Xu, Junlong Song, Yongcan Jin, Michael Wink, and Guoqiu Wu |
| Summary: | Antimicrobial peptides (AMPs) are typical cell penetrating peptides (CPPs) that intercalate into biomembranes and exhibit broad activities. We designed a triple fusion protein consisting of an AMP, Ib-AMP4 at the N-terminus, a fluorescent GFP probe in the center, and the tumor-targeting peptide P1c at the other terminus. After purification from E. coli, the interaction between the Ib-AMP4-GFP-P1c fusion protein (IGP) and the lipid membrane was characterized. Experiments using isothermal titration calorimetry (ITC) and quartz crystal microbalance with dissipation (QCM-D) demonstrated that IGP proteins spontaneously bound the lipid bilayer with a maximal molar ratio of 1:52 (protein:lipid). Furthermore, transmission electron microscopy (TEM) confirmed that the IGP protein was present in the liposome membrane. After decoration with IGP proteins, the DOPC:DOPG liposomes were applied to cancer cells. Microscopy and flow cytometry reveal that the decorated liposomes selectively bound integrin αvβ3-positive A549 cells. In addition, compared with the common chemical conjugation method, the reported method seemed to be superior in certain aspects, such as simple sample preparation and cost-effectiveness. Next, the IGP protein was applied to decorate red blood cell (RBC) liposomes for targeted delivery in both in vitro and in vivo applications. The IGP-decorated RBC liposomes preferentially targeted integrin αvβ3 expressing A549 cancer cells. The in vivo imaging showed that IGP-decorated RBC liposomes were concentrated in tumor tissue and were primarily metabolized by the liver and kidney. |
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| Item Description: | Publication date: December 16, 2019 Gesehen am 24.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1520-4812 |
| DOI: | 10.1021/acs.bioconjchem.9b00798 |