title: Quantitative evaluation of bioorthogonal chemistries for surface functionalization of nanoparticles.
abstract: We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.
authors.affiliation: DTU Nanotech, Department of Micro- and Nanotechnology, Technical University of Denmark, Building 423 2800 Lyngby, Denmark.
authors.forename: Lise N
authors.initials: LN
authors.lastname: Feldborg
authors.forename: Rasmus I
authors.initials: RI
authors.lastname: Jølck
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andresen
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D057930:Click Chemistry; D006801:Humans; D019811:Hydroxylamine / Q000737:chemistry*; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis*; D010455:Peptides / Q000138:chemical synthesis*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000447:Aldehydes; D008081:Liposomes; D010091:Oximes; D010455:Peptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D019811:Hydroxylamine; D011092:Polyethylene Glycols