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.

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.

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