Development of a bifunctional immunoliposome system for combined drug delivery and imaging in vivo

Feng, Bin; Tomizawa, Kazuhito; Michiue, Hiroyuki; Han, Xiao Jian; Miyatake, Shin; Matsui, Hideki

doi:10.1016/j.biomaterials.2010.01.086

Cited by 32 publications

(34 citation statements)

References 30 publications

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“…The values for incorporation ratios in parenthesis were calculated by us based on following equation: maleimide lipid molar ratio (of the total lipids in the liposomes)×0.55 (ratio facing outward from the membrane) (Eq. 1 in Chart 1) with the assumption of a 100% reaction yield, which means that all of the anchors contained an attached ligand [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] . mAb: monoclonal antibody, r.t.: room temperature, n.d.; no data.…”

Section: Methodsmentioning

confidence: 99%

“…33) Most literature reports do not provide these two values or provide sufficiently accurate values to permit the surface topologies to be evaluated. Instead, bioactivities are evaluated with reference to differences in the composition of liposomal lipids [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] (Table 1). The affinity of a liposome toward binding and its pharmacokinetics are related to its surface topology, 29,30,[48][49][50] which is defined as the ratio of the density of the surface ligand and PEG that are located on the liposomal surface.…”

Section: -9)mentioning

confidence: 99%

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Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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The surface topology of ligands on liposomes is an important factor in active targeting in drug delivery systems. Accurately evaluating the density of anchors and bioactive functional ligands on a liposomal surface is critical for ensuring the efficient delivery of liposomes. For evaluating surface ligand density, it is necessary to clarify that on the ligand-modified liposomal surfaces, some anchors are attached to ligands but some are not. To distinguish between these situations, a key parameter, surface anchor density, was introduced to specify amount of total anchors on the liposomal surface. Second, the parameter reaction yield was introduced to identify the amount of ligand-attached anchors among total anchors, since the conjugation efficiency is not always the same nor 100%. Combining these independent parameters, we derived: incorporation ratio surface anchor density reaction yield. The term incorporation ratio defines the surface ligand density. Since the surface anchor density represents the density of polyethylene glycol (PEG) on the surfaces in most cases, it also determines liposomal function. It is possible to accurately characterize various PEG and ligand densities and to define the surface topologies. In conclusion, this quantitative methodology can standardize the liposome preparation process and qualify the modified liposomal surfaces.Key words active targeting; surface ligand density; incorporation ratio; surface anchor density; reaction yield; surface topology Nanotechnology has the capability to deliver drugs to specific cell types, but it is important to maximize therapeutic effects and minimize unexpected adverse effects, for this technology to be effectively used.1-4) In using nanoparticles for specific drug delivery, they need to have both a stealth function to prevent non-specific recognition by the reticuloendothelial system (RES), 5,6) and an active targeting function to allow them to bind to the specific cell type of interest. 7-9)Polyethylene glycol (PEG) modification is frequently used to confer a stealth function to nanoparticles. 5,6,10) For active targeting, specific ligands for bioactive molecules such as nucleic acids, peptides, proteins, and antibodies are attached to the surface of nanoparticles via a PEG spacer.11) Many attempts have been made to develop various types of specific ligands for use in active targeting, which is critical for targeting non-fenestrated tissues such as the brain, lung and related tissues. [12][13][14] The procedures used to prepare ligands that are used in modifying nanoparticles are relatively complicated because this increases the number of steps in the preparation process that can lead to conditions where ligand molecules can be unstable.15) Therefore, optimal reaction (modification) conditions and methods for quantifying the density of the attached ligand that is attached to the nanoparticles need to be evaluated precisely.Problems are usually encountered in evaluating both the density of the liposomal ligands and the PEG, since a variety of m...

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Section: Methodsmentioning

confidence: 99%

Section: -9)mentioning

confidence: 99%

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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“…It would be interesting to develop a membrane-impermeable substrate for this luciferase. 31,32 We used the CMV promoter for expression of the chimeric membrane protein in CHO-K1 cells. Ohomiya et al 7,19 studied the effect of promoters on the expression level of DL in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

Bioluminescence Assay for Detecting Cell Surface Membrane Protein Expression

Kato

Chiba

et al. 2011

ASSAY and Drug Development Technologies

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We have developed a method to measure the amounts of cell surfaceexpressed membrane proteins with bioluminescence. Dinoflagellate luciferase was expressed on the surface of a mammalian cell as a chimeric fusion protein with a membrane protein of interest. Using a membrane-impermeable substrate to quantify the membrane-displayed luciferase, the expression of the membrane protein on the cell surface was determined. By inclusion of a quenching step for the luminescent activity of luciferase on the cell surface, we were able to monitor the membrane protein expression kinetics by measuring the luminescence recovery from the cell surface after quenching. The reported methods provide a convenient way to monitor the kinetics of expression and transport of membrane proteins to the cell surface. It is applicable to the high-throughput analysis of drugs or drug candidates concerning their effects on membrane protein expression.

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“…Поэтому в по-следнее время изучают векторные контейнерные системы на основе антител к опухоль-ассоциированным белкам, таким как Her-2 [113], EGFR [114], GFAP и Cx-43 [102], VEGF [115] и VEGFR2 [116]. Векторизация контейнеров моноклональными антителами позволяет получить си-стему для адресной доставки лекарств.…”

Section: высокоселективные контейнерные системыunclassified