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

• Published in: Journal of drug targeting Vol. 16; no. 7-8; pp. 596 - 600
• Main Authors: Sawant, Rupa R., Sawant, Rishikesh M., Kale, Amit A., Torchilin, Vladimir P.
• Format: Journal Article
• Language: English
• Published: Abington Informa UK Ltd 01.01.2008; Taylor & Francis
• Subjects: Biological and medical sciences; cell-penetrating peptide; Drug Carriers; Drug Delivery Systems; Fluorescence Resonance Energy Transfer; General pharmacology; intracellular delivery; Ligands; Medical sciences; Micelles; Nanoparticles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polyethyleneglycol-phosphatidylethanolamine; Polymeric micelles; TAT peptide; Intracellular transport; Phosphatidylethanolamine; Pharmaceutical technology; Targeting; Cell penetrating peptide; Ligand; Control release polymer; Interaction; TAT peptide; Micelle; intracellular delivery; In vitro; cell-penetrating peptide; Ethylene oxide polymer; Target; polyethyleneglycol-phosphatidylethanolamine; Polymeric micelles
• ISSN: 1061-186X; 1029-2330
• DOI: 10.1080/10611860802230240

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-PEG1000-PE or TATp-PEG3400-PE) than the PEG block in the main micelle-forming material (PEG750-PE and/or PEG2000-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 PEG750-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.