Phosphatase-Mediated Hydrolysis of Linear Polyphosphates.

Polyphosphates are a group of phosphorus (P) containing molecules that are produced by a wide range of microorganisms and human activities. Although polyphosphates are ubiquitous in aquatic environments and are of environmental significance, little is known about their transformation and cycling. This study characterized the polyphopshate-hydrolysis mechanisms of several representative phosphatase enzymes and evaluated the effects of polyphosphate chain length, light condition, and calcium (Ca).

Leakage kinetics of the liposomal chemotherapeutic agent Doxil: The role of dissolution, protonation, and passive transport, and implications for mechanism of action.

Doxil, a liposomal formulation of the chemotherapeutic drug doxorubicin, is FDA-approved for multiple indications. Doxil liposomes are designed to retain doxorubicin in circulation, minimize clearance by the mononuclear phagocyte system, and limit uptake in healthy tissue. Although pharmacokinetic data and survival statistics from clinical trials provide insight into distribution and efficacy, many details of the mechanism of action remain unresolved, despite the importance in translating liposome-based drug delivery systems to other molecules and cargo.

Tumor accumulation of liposomal doxorubicin in three murine models: Optimizing delivery efficiency.

Systemic drug delivery to a solid tumor involves a sequence of steps that determine efficacy and survival. Extravasation from circulation at the tumor site is a critical step in this sequence since it regulates how much of the drug accumulates in the tumor. Despite its importance in determining outcomes, extravasation from circulation remains a "black box.

Brain microvascular endothelial cells resist elongation due to curvature and shear stress.

The highly specialized endothelial cells in brain capillaries are a key component of the blood-brain barrier, forming a network of tight junctions that almost completely block paracellular transport. In contrast to vascular endothelial cells in other organs, we show that brain microvascular endothelial cells resist elongation in response to curvature and shear stress. Since the tight junction network is defined by endothelial cell morphology, these results suggest that there may be an evolutionary advantage to resisting elongation by minimizing the total length of cell-cell junctions per unit length of vessel.