The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells.

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The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells. Abstract Text:

Surface architecture of pharmaceutical nanocarriers (using polymeric micelles as an example) and the length of the spacer group through which specific ligand is attached to the carrier surface determine the interaction of ligand-bearing nanocarrier with cells. We have prepared surface-modified polyethyleneglycol-phosphatidylethanolamine (PEG-PE) micelles containing TATp attached to PEG-PE with a PEG block longer or shorter (TATp-PEG(1000)-PE or TATp-PEG(3400)-PE) than the PEG block in the main micelle-forming material (PEG(750)-PE and/or PEG(2000)-PE). The length of the PEG spacer in TATp-PEG-PE should allow for a non-hindered interaction of TATp with the cell surface, but it should not be too long to allow for the conformational "folding in" of TATp moiety inside the PEG globule making it unable to interact with the cells. The "folding in" of the ligand attached to an unnecessary long PEG spacer was further supported by the fluorescence resonance energy transfer (FRET) study between fluorescently labeled lipid 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (NBD-PE) inserted into the core of PEG(750)-PE micelles and micelle-incorporated rhodamine-labeled TATp-PEG-PE. Micelles containing rhodamine-labeled TATp-PEG-PE with the longest PEG spacer (3400 Da) demonstrated strongly enhanced quenching of NBD-PE fluorescence with rhodamine-TATp confirming the "folding in" of TATp moiety into PEG globule bringing it closer to the micelle core-incorporated NBD.

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The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of drug targeting

VOLUME: 16

Page Numbers: 596-600

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ISSN: 1029-2330

DAY: 7

MONTH: Aug

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 9312476

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Grant and Affiliation Information for The architecture of ligand attachment to nanocarriers controls their specific interaction with target cells.

AFFILIATION: Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.

Country: England

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MEDLINETA: J Drug Target

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