Measurement of membrane tension of free standing lipid bilayers via laser-induced surface deformation spectroscopy.

Non-invasive measurement of the membrane tension of free-standing black lipid membranes (BLMs), with sensitivity on the order of µN m(-1), was achieved using laser-induced surface deformation (LISD) spectroscopy. A BLM was vertically formed via the folding method and aqueous phases with different refractive indices were added on each side in order to induce radiation pressure by a laser beam. The dynamic response of the deformed BLMs was measured under periodic intensity modulation and their tensions could be estimated. The dependence of membrane tension on the cholesterol concentration of BLMs composed of phosphatidylcholine and phosphatidylethanolamine was investigated, with the membrane tension increasing from 1.3 µN m(-1) to 68.1 µN m(-1) when the cholesterol concentration increased from zero to 33%. These tension values are much smaller than some of those previously reported, because this method does not suppress membrane fluctuation unlike other conventional methods. Our LISD system can be a promising tool for the measurement of membrane tension in BLMs.

Design and use of silica-containing redox nanoparticles, siRNPs, for high-performance peritoneal dialysis.

The prevention of encapsulating peritoneal sclerosis (EPS) and the enhancement of dialysis efficiency are two important strategies that can improve the quality of life of patients undergoing peritoneal dialysis. We have thus far developed bionanoparticles that effectively scavenge reactive oxygen species (redox nanoparticles; RNPs). The objective of this study was to apply RNPs as a component of dialysate to reduce oxidative stress. Porous silica nanoparticles were combined with RNPs to enhance the effective adsorption capacity of low-molecular weight (LMW) compounds. The silica-containing RNPs (siRNPs) were confirmed to statistically decrease the level of creatinine and blood urea nitrogen in vivo. EPS model rats that underwent an intraperitoneal injection of chlorhexidine gluconate exhibited dysfunction of the peritoneal membrane. siRNP administration did not result in dysfunction of the peritoneal membrane. An LMW nitroxide compound, TEMPOL, also showed a weak peritoneal protective effect, although its efficiency was limited. No blood uptake of siRNPs was observed when they were administered into the peritoneal cavity. However, LMW-TEMPOL diffused into the blood stream, which might have decreased its effective concentration in the peritoneal cavity and led to adverse effects across the entire body. Considering these results, siRNPs are expected to be a new multi-functional nanomaterial for high performance peritoneal dialysis.

Pharmacokinetics of core-polymerized, boron-conjugated micelles designed for boron neutron capture therapy for cancer.

Core-polymerized and boron-conjugated micelles (PM micelles) were prepared by free radical copolymerization of a PEG-b-PLA block copolymer bearing an acetal group and a methacryloyl group (acetal-PEG-b-PLA-MA), with 1-(4-vinylbenzyl)-closo-carborane (VB-carborane), and the utility of these micelles as a tumor-targeted boron delivery system was investigated for boron neutron capture therapy (BNCT). Non-polymerized micelles (NPM micelles) that incorporated VB-carborane physically showed significant leakage of VB-carborane (ca. 50%) after 12 h incubation with 10% fetal bovine serum (FBS) at 37 °C. On the other hand, no leakage from the PM micelles was observed even after 48 h of incubation. To clarify the pharmacokinetics of the micelles, (125)I (radioisotope)-labeled PM and NPM micelles were administered to colon-26 tumor-bearing BALB/c mice. The (125)I-labeled PM micelles showed prolonged blood circulation (area under the concentration curve (AUC): 943.4) than the (125)I-labeled NPM micelles (AUC: 495.1), whereas tumor accumulation was similar for both types of micelles (AUC(PM micelle): 249.6, AUC(NPM micelle): 201.1). In contrast, the tumor accumulation of boron species in the PM micelles (AUC: 268.6) was 7-fold higher than the NPM micelles (AUC: 37.1), determined by ICP-AES. Thermal neutron irradiation yielded tumor growth suppression in the tumor-bearing mice treated with the PM micelles without reduction in body weight. On the basis of these data, the PM micelles represent a promising approach to the creation of boron carrier for BNCT.