Assessing the long-term stability of anti-drug antibodies in method validation: what is the added value?

The stability of analytes in biological matrices is a critical parameter assessed under bioanalytical method validations. Assessing the stability of anti-drug antibodies (ADA) is, however, not evident given the polyclonal antibody response and the practicality of obtaining reference material from human subjects. Moreover, the same argument that different test articles exhibit different stabilities does not translate to polyclonal antibodies, for which there is a body of literature supporting the stability of human antibodies in undiluted human biological matrix for several years.

Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia.

Gold nanoparticles have emerged as promising tools for cancer research and therapy, where they can promote thermal killing. The molecular mechanisms underlying these events are not fully understood. The geometry and size of gold nanoparticles can determine the severity of cellular damage.

Modulation of inflammatory signaling and cytokine release from microglia by celastrol incorporated into dendrimer nanocarriers.

Aim: This study investigates the capacity of a potent anti-inflammatory nanomedicine, celastrol, incorporated into poly(amidoamine) dendrimers, to inhibit endotoxin-mediated signaling in microglia.

Materials & Methods: Celastrol was incorporated into amino (Cel/G4-NH(2)) and hydroxyl (Cel/G4-OH) terminus poly(amidoamine) (G4) dendrimers. Cell viability, release of nitric oxide, IL-6, TNF-α and activation of MAPK (e.

A novel mouse model of Alzheimer's disease with chronic estrogen deficiency leads to glial cell activation and hypertrophy.

The role of estrogens in Alzheimer's disease (AD) involving β-amyloid (Aβ) generation and plaque formation was mostly tested in ovariectomized mice with or without APP mutations. The aim of the present study was to explore the abnormalities of neural cells in a novel mouse model of AD with chronic estrogen deficiency. These chimeric mice exhibit a total FSH-R knockout (FORKO) and carry two transgenes, one expressing the β-amyloid precursor protein (APPsw, Swedish mutation) and the other expressing presenilin-1 lacking exon 9 (PS1Δ9).

Microglial response to gold nanoparticles.

Given the emergence of nanotherapeutics and nanodiagnostics as key tools in today's medicine, it has become of critical importance to define precisely the interactions of nanomaterials with biological systems and to characterize the resulting cellular response. We report here the interactions of microglia and neurons with gold nanoparticles (GNPs) of three morphologies, spheres, rods, and urchins, coated with poly(ethylene glycol) (PEG) or cetyl trimethylammonium bromide (CTAB). Microglia are the resident immune cells of the brain, primarily involved in surveillance, macrophagy, and production of cytokines and trophic factors.

The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity.

Among various hydrogels able to form monodisperse and stable nanoparticles (20-30 nm) are those with pullulan-bearing cholesteryl moieties (CHP). These nanoparticles can interact with soluble proteins through hydrophobic bonding. The objectives of this study were to investigate whether CHP nanogels would interact with oligomeric forms of the 42 amino acid variant of beta-amyloid (Abeta(1-42)) and if the formation of CHP-Abeta(1-42) oligomer entities will reduce cytotoxicity of Abeta(1-42) in primary cortical cells and microglial (N9) cells.

Molecular imaging of lipid peroxyl radicals in living cells with a BODIPY-alpha-tocopherol adduct.

An increasing number of reports discuss the role reactive oxygen species (ROS) have in cellular pathologies and cellular signaling processes. Critical to elucidating the underlying chemical mechanism behind these biological processes is the development of novel sensors and reporters with chemical sensitivity and, more importantly, molecular specificity, enabling the spatial and temporal monitoring of a specific ROS concentration in live cells. Here we report for the first time on the application of BODIPY-alpha-Tocopherol adduct (B-TOH), a novel lipophilic fluorescent antioxidant indicator, toward detection of peroxyl radicals in model lipid membranes and their imaging in the lipid membrane of live cells.