Gold nanoparticles can enhance the biological effective dose of radiation delivered to tumors, but few data exist to quantify this effect. The purpose of this project was to build a Monte Carlo simulation model to study the degree of dose enhancement achievable with gold nanoparticles. A Monte Carlo simulation model was first built using Geant4 code. An Ir-192 brachytherapy source in a water phantom was simulated and the calculation model was first validated against previously published data. We then introduced up to 10(13) gold nanospheres per cm(3) into the water phantom and examined their dose enhancement effect. We compared this enhancement against a gold-water mixture model that has been previously used to attempt to quantify nanoparticle dose enhancement. In our benchmark test, dose-rate constant, radial dose function, and two-dimensional anisotropy function calculated with our model were within 2% of those reported previously. Using our simulation model we found that the radiation dose was enhanced up to 60% with 10(13) gold nanospheres per cm(3) (9.6% by weight) in a water phantom selectively around the nanospheres. The comparison study indicated that our model more accurately calculated the dose enhancement effect and that previous methodologies overestimated the dose enhancement up to 16%. Monte Carlo calculations demonstrate that biologically-relevant radiation dose enhancement can be achieved with the use of gold nanospheres. Selective tumor labeling with gold nanospheres may be a strategy for clinically enhancing radiation effects.

MUC1-C oncoprotein is associated with colon, breast, ovarian, lung and pancreatic cancers. MUC1-C interacts with intracellular proteins to elicit signaling cascades that induce cell proliferation and tumor growth. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ), an E3 ubiquitin ligase, is an inhibitor of MUC1-C-mediated cell proliferation. PPARγ does so by binding to and inducing MUC1-C proteasome-dependent degradation that was independent of PPARγ transcriptional activity. Lys134 residue was found to be critically important for PPARγ-mediated MUC1-C degradation, as it terminated MUC1-C-mediated cell proliferation. These findings demonstrate PPARγ induces MUC1-C ubiquitination and degradation that is critical to terminate MUC1-C signaling pathway-elicited cancer.

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PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family, which plays a critical role in inhibiting cell proliferation and tumorigenesis, while the molecular mechanism is still unclear. Here we report that PPARα serves as an E3 ubiquitin ligase to govern Bcl2 protein stability. PPARα physically bound to Bcl2 protein. In this process, PPARα/C102 was critical for PPARα binding to BH3 domain of Bcl2, subsequently, PPARα transferred K48-linked polyubiquitin to lysine-22 site of Bcl2 resulting in its ubiquitination and proteasome-dependent degradation. Importantly, overexpression of PPARα enhanced cancer cell chemotherapy sensitivity. In contrast, silenced PPARα decreased this event. These findings revealed a novel mechanism of PPARα governed endogenous Bcl2 protein stability leading to reduced cancer cell chemoresistance, which provides a potential drug target for cancer treatment.

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A facile ligand exchange approach for surface‐functionalized ZnS nanoparticles (NPs) with 5‐(2‐methacryloylethyloxymethyl)‐8‐quinolinol (MQ) is described. The MQ–ZnS NPs, with a cubic crystal structure, have the same diameter as ZnS NPs without MQ about 3.0 nm. The MQ–ZnS NPs exhibit strong fluorescence emission at about 500 nm and a high photoluminescence (PL) quantum yield (QY), up to 40%, with a decreasing ratio of MQ to ZnS NPs. The PL decay study reveals that the lifetimes of the different MQ–ZnS NPs with a single exponential decay are in the nanosecond time domain for emission at about 500 nm, which is obviously different from that of ZnS NPs with a biexponential decay for defect‐state emission at 420 nm. The functionalized MQ–ZnS NPs are successfully incorporated into the polymer matrix by in situ bulk polymerization to fabricate transparent bulk nanocomposites with good thermal stability and processability. Transmission electron microscopy results show that the NPs are uniformly dispersed in the polymer matrix without aggregation. The good PL properties of MQ–ZnS NPs are preserved in the bulk nanocomposites. It is observed that the nanocomposites have red‐shifted excitation and emission wavelengths compared with those of both the polymer matrix and MQ–ZnS NPs, possibly because of the cooperative interaction between MQ–ZnS NPs and the polymer matrix with blue emission.

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