Lipid-Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer.

Neuropeptides are small neuronal signaling molecules that act as neuromodulators for a variety of neural functions including analgesia, reproduction, social behavior, learning, and memory. One of the endogenous neuropeptides-Met-Enkephalin (Met-Enk), has been shown to display an inhibitory effect on cell proliferation and differentiation. Here, a novel lipid-modification approach is shown to create a small library of neuropeptides that will allow increased bioavailability and plasma stability after systemic administration. It is demonstrated, on an experimental model of human pancreatic adenocarcinoma, that lipid conjugation of Met-Enk enhances its tumor suppression efficacy compared to its nonlipidated counterparts, both in vitro and in vivo. More strikingly, the in vivo studies show that a combination therapy with a reduced concentration of Gemcitabine has suppressed the tumor growth considerably even three weeks after the last treatment.

Supported bilayers formed from different phospholipids on spherical silica substrates.

Spherical supported bilayer membranes (SS-BLMs) are very attractive candidates in modern bioanalytics and biorecognition studies. A uniform, facile method of preparing different SS-BLMs on silica beads is reported. Confocal fluorescence microscopy and cryo-TEM imaging have been used to characterize these SS-BLMs. Thermal analysis data and FRAP experiments show that the bilayer properties of the SS-BLM are consistent with those of lipid vesicles from which they are formed. The possibility of modulating the size, lipid type and functionality, and mechanical stability makes these rigid liposomes very attractive candidates in biosensors, drug screening, and gene delivery-related applications. This is especially true in work with native vesicle membranes derived from living cells because the existing methods can only accommodate anionic membranes to a limited extent.