Tumor-specific gene transfer with receptor-mediated nanocomplexes modified by polyethylene glycol shielding and endosomally cleavable lipid and peptide linkers.

Synthetic nanoparticle formulations have the potential for tumor-targeted gene delivery. Receptor-targeted nanocomplex (RTN) formulations comprise mixtures of cationic liposomes and targeting peptides that self-assemble on mixing with nucleic acids. RTN formulations were prepared containing different polyethylene glycol (PEG)ylated lipids with esterase-cleavable linkers (e.

Stabilized integrin-targeting ternary LPD (lipopolyplex) vectors for gene delivery designed to disassemble within the target cell.

Recent research in the field of nonviral gene delivery vectors has focused on preparing nanoparticles that are stabilized by the incorporation of a PEG coating and where one of the vector components is also cleavable. Here,we describe the synthesis, formulation, transfection properties, and biophysical studies of a PEG-stabilized ternary lipopolyplex vector in which, for the first time, both the lipid and peptide components are designed to be cleaved once the vector has been internalized. A series of cationic lipids, bearing short tri- or hexaethylene glycol groups, attached to the headgroup via an ester linkage, has been prepared.

A receptor-targeted nanocomplex vector system optimized for respiratory gene transfer.

Synthetic vectors for cystic fibrosis (CF) gene therapy are required that efficiently and safely transfect airway epithelial cells, rather than alveolar epithelial cells or macrophages, and that are nonimmunogenic, thus allowing for repeated delivery. We have compared several vector systems against these criteria including GL67, polyethylenimine (PEI) 22 and 25 kd and two new, synthetic vector formulations, comprising a cationic, receptor-targeting peptide K(16)GACSERSMNFCG (E), and the cationic liposomes (L) DHDTMA/DOPE or DOSEP3/DOPE. The lipid and peptide formulations self assemble into receptor-targeted nanocomplexes (RTNs) LED-1 and LED-2, respectively, on mixing with plasmid (D).

Multivalence and spot heterogeneity in microarray-based measurement of binding constants.

Microarray technology is increasingly used for a miniaturised and parallel measurement of binding constants. In microarray experiments heterogeneous functionalization of surfaces with capture molecules is a problem commonly encountered. For multivalent ligands, especially, however, binding is strongly affected by receptor density.

Peptide microarrays for the detection of molecular interactions in cellular signal transduction.

The formation of protein complexes is a hallmark of cellular signal transduction. Here, we show that peptide microarrays provide a robust and quantitative means to detect signalling-dependent changes of molecular interactions. Recruitment of a protein into a complex upon stimulation of a cell leads to the masking of an otherwise exposed binding site.

Determination of binding constants on microarrays with confocal fluorescence detection.

Confocal laser scanning microscopy was employed for the determination of binding constants of receptor-ligand interactions in a microarray format. Protocols for a localized immobilization of amine containing substances on glass via GOPTS (3-glycidyloxypropyl)trimethoxysilane) were optimized with respect to the detection of ligand binding by fluorescence. Compatibility with miniaturization by nanopipetting devices was ensured during all steps.

Modulation of neuronal activity by the endogenous pentapeptide QYNAD.

Inflammation and demyelination both contribute to the neurological deficits characteristic of multiple sclerosis. Neurological dysfunctions are attributable to inflammatory demyelination and, in addition, to soluble factors such as nitric oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in the cerebrospinal fluid of patients with demyelinating disorders, has been proposed to promote axonal dysfunction by blocking sodium channels.