Abstract:
:High-functionality and -quality (HFQ) lipids have a discrete molecular weight and good water dispersibility and can be produced by solid-phase peptide synthesis. Therefore, HFQ lipids are a promising material for the preparation of ligand-grafted PEGylated liposomes. Recently, we have reported serine-glycine repeated peptides ((SG) n) as a spacer of HFQ lipids and to substitute a conventional PEG spacer. We demonstrated the advantage of using (SG) n spacers for peptide ligand presentation on the liposomal surface in vitro; however, the use of (SG) n spacers in ligand-grafted PEGylated liposomes in vivo has not been validated. The aim of this study was to validate the in vivo targeting ability of HFQ lipid-grafted PEGylated liposomes. We synthesized lipids containing GRGDS (RGD-(SG) n-lipid) to target integrin αvβ3 and prepared RGD-(SG) n/PEGylated liposomes. Subsequently, their cellular uptake characteristics in murine colon carcinoma (Colon-26) cells were evaluated. Two-color imaging of liposomes and tumor blood vessels following tissue clearing was performed to examine the spatial intratumoral distribution of liposomes. RGD-(SG)5/PEGylated liposomes were selectively associated with the cells in vitro. In vivo analysis of intratumoral distribution following tissue clearing revealed the superior targeting ability of RGD-(SG)5/PEGylated liposomes compared with that of conventional RGD-PEG2000/PEGylated liposomes for both tumor tissues and tumor blood vessels. We successfully synthesized RGD-HFQ lipids to prepare RGD-grafted PEGylated liposomes for the efficient targeting of integrin αvβ3-expressing cells. To the best of our knowledge, this is the first report of the intratumoral distribution of ligand-grafted PEGylated liposomes by two-color imaging following tissue clearing.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Suga T,Kato N,Hagimori M,Fuchigami Y,Kuroda N,Kodama Y,Sasaki H,Kawakami Sdoi
10.1021/acs.molpharmaceut.8b00476subject
Has Abstractpub_date
2018-10-01 00:00:00pages
4481-4490issue
10eissn
1543-8384issn
1543-8392journal_volume
15pub_type
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