Radiosensitization of tumor cells through endoplasmic reticulum stress induced by PEGylated nanogel containing gold nanoparticles.

High atomic number molecules, such as gold and platinum, are known to enhance the biological effect of X-irradiation. This study was aimed to determine the radiosensitizing potential of PEGylated nanogel containing gold nanoparticles (GNG) and the cellular mechanism involved. GNG pretreatment increased the levels of reproductive cell death and apoptosis induced by X-irradiation. GNG accumulated in cytoplasm and increased the expression of endoplasmic reticulum (ER) stress-related protein. GNG suppressed the repair capacity of DNA after X-irradiation by down-regulating DNA repair-related proteins. Our results suggest that GNG radiosensitized cells by enhancing apoptosis and impairing DNA repair capacity via ER stress induction.

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.

Large payloads of gold nanoparticles into the polyamine network core of stimuli-responsive PEGylated nanogels for selective and noninvasive cancer photothermal therapy.

A biocompatible photothermal nanomedicine based on a PEGylated nanogel containing gold nanoparticles (GNPs) in a cross-linked network core of stimuli-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PEAMA) gel for cancer photothermal therapy (PTT) was prepared through the reduction of Au(iii) ions without any reducing agents. The influence of the reduction conditions, such as pH, temperature, and N/Au ratio (molar ratio of the amino groups in the PEGylated nanogel to the Au(iii) ions), on the formation of the GNPs in the stimuli-responsive PEAMA gel core (reducing environment) was also studied. Note that the PEGylated nanogel containing GNPs prepared at pH 6, 60 degrees C and N/Au = 1 (PEGylated GNG (1)) was found to have the highest GNP-loading capacity with a diameter of about 8 nm, as observed by TEM; viz., about 27 GNPs formed in a single PEAMA gel core. PEGylated GNG (1) showed a remarkable photothermal efficacy (DeltaT = 7.7 degrees C) under irradiation with Ar ion (Ar(+)) laser (514.5 nm) at a fluence of 39 W cm(-2) for 6 min (14 kJ cm(-2)). Note that PEGylated GNG (1) showed non-cytotoxicity in the absence of irradiation with Ar(+) laser (480 microg mL(-1): > 90% cell viability), whereas pronounced cytotoxicity (IC(50) = 110 microg mL(-1)) was observed for PEGylated GNG (1) under irradiation with Ar(+) laser at a fluence of 26 W cm(-2) for 5 min (7.8 kJ cm(-2)), because of the heat-generation from the GNPs in the cells, which resulted in selective and noninvasive cancer PTT. Thus, PEGylated GNG (1), which has a high GNP-loading capacity, would be a promising nanomedicine for cancer PTT.

Characterization of a glucose sensor prepared by electropolymerization of pyrroles containing a tris-bipyridine osmium complex.

A glucose sensor was developed by electrocopolymerization using pyrroles containing a tris-bipyridine (bpy) osmium complex (Os-py), pyrrole (py), pyrrole propanoic acid (PPA) and glucose oxidase (GOx) to improve the key performance characteristics, such as the sensitivity, selectivity, and long-term stability. Tris-bipyridine osmium pyrrole complexes with four different methylene moieties were utilized to correlate the methylene length with the glucose sensor performance. The electrocatalytic response of glucose was clearly observed at electrodes modified with Os-py, except for the electrode immobilized with the Os-py complex containing the shortest methylene moiety. The current response to glucose increased up to a concentration of 100 mmol dm(-3). The electrocatalytic response to glucose at the [Os(bpy)(2)(py(6)-bpy)](2+/3+)/py/PPA/GOx electrode was stable for more than 100 days. Dissolved oxygen and potential interference compounds (ascorbic acid, uric acid, and acetaminophen) minimally perturbed the current response to glucose at the [Os(DM-bpy)(2)(py(6)-bpy)](2+/3+)/py/PPA/GOx electrode. Based on these results, a longer methylene moiety appears to improve the performance characteristics of a glucose sensor fabricated via the electropolymerization of tris-bipyridine osmium pyrrole complexes.