Ligand-based targeted delivery of a peptide modified nanocarrier to endothelial cells in adipose tissue
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概要
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Ligand-based targeted delivery is an emerging platform in nanomedicine. We report herein on a peptide modified nanocarrier for a ligand-based targeted delivery system. The liposomal surface of the carrier was first modified with a linear peptide, followed by an adipose tissue-specific circular peptide (KGGRAKD) via a polyethylene glycol (PEG) spacer. To evaluate the specificity of the carrier, we purified primary cells from the endothelium of adipose tissue. The liposomes bound only to isolated primary cultured endothelial cells derived from inguinal adipose tissue (pcEC-IWAT) and not to other endothelial cell lines, such as MBEC-4 and MFLM-4. Cellular uptake was confirmed both qualitatively and quantitatively by confocal laser scanning microscopy (CLSM) and flow cytometry. The mechanism for the intracellular uptake of tPep-PEG-LPs into pcEC-IWAT, as evidenced by three independent experiments, involves saturation of receptor binding sites by excess free peptide, the blocking of receptors by an anti-prohibitin antibody and low temperature (4℃) experiments, resulting in the inhibition of up-take of tPep-PEG-LPs into pcEC-IWAT, suggesting that receptor mediated endocytosis largely contributed to the observed cellular uptake. A co-localization study using double labeled modified liposomes (lipid membrane: NBD-DOPE and aqueous phase: rhodamine) indicated that a predominant part of tPep-PEG-LPs was found without co-localization with lysosomes and retained their intactness. The selective delivery of tPep-PEG-LPs to endothelial cells in adipose tissue represents a potential approach for the design of diverse nanocarrier-based targeted delivery systems for targeting the vasculature in adipose tissue.
- 2010-10-15
著者
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原島 秀吉
北大院・薬学研究科
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梶本 和昭
北海道大学大学院薬学研究院
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Akita Hidetaka
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Shim Chang
Faculty Of Pharmaceutical Sciences University Of Tokyo : (present Address) College Of Pharmacy Seoul
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SHIGENOBU Kohki
Faculty of Pharmaceutical Sciences, University of Tokyo
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Harashima Hideyoshi
Department Of Pharmacokinetics And Pharmaceutics Graduate School Of Pharmaceutical Sciences The Univ
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Akita Hidetaka
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Kajimoto Kazuaki
Department Of Epidemiology Divisions Of Preventive Medicine
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Kajimoto Kazuaki
Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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