Fe Core-Carbon Shell Nanoparticles as Advanced MRI Contrast Enhancer.

The aim of this study is to fabricate a hybrid composite of iron (Fe) core-carbon (C) shell nanoparticles with enhanced magnetic properties for contrast enhancement in magnetic resonance imaging (MRI). These new classes of magnetic core-shell nanoparticles are synthesized using a one-step top-down approach through the electric plasma discharge generated in the cavitation field in organic solvents by an ultrasonic horn. Transmission electron microscopy (TEM) observations revealed the core-shell nanoparticles with 10-85 nm in diameter with excellent dispersibility in water without any agglomeration. TEM showed the structural confirmation of Fe nanoparticles with body centered cubic (bcc) crystal structure. Magnetic multi-functional hybrid composites of Fe core-C shell nanoparticles were then evaluated as negative MRI contrast agents, displaying remarkably high transverse relaxivity (r2) of 70 mM-1·S-1 at 7 T. This simple one-step synthesis procedure is highly versatile and produces desired nanoparticles with high efficacy as MRI contrast agents and potential utility in other biomedical applications.

Prostate cancer-specific thermo-responsive polymer-coated iron oxide nanoparticles.

Thermo-responsive poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (PMNPs) were developed and conjugated with prostate cancer-specific R11 peptides for active targeting and imaging of prostate cancer. The stable nanoparticles with an average diameter of 100 nm and surface charge of -27.0 mV, had a lower critical solution temperature of 40 °C. Magnetic characterization showed that the nanoparticles can be recruited using a magnetic field and possess superparamagnetic behavior even after R11 conjugation. In vitro cell studies demonstrated that R11-conjugated PMNPs (R11-PMNPs) were compatible with human dermal fibroblasts and normal prostate epithelial cells to all tested concentrations up to 500 µg/ml after 24 h of incubation. Moreover, the nanoparticles were taken up by prostate cancer cells (PC3 and LNCaP) in a dose-dependent manner, which was higher in case of R11-PMNPs than PMNPs. Further, in vivo biodistribution of the nanoparticles showed significantly more R11-PMNPs accumulation in tumors than other vital organs unlike PMNPs without R11 conjugation. Moreover, R11-PMNPs decreased 30% magnetic resonance T2 signal intensity in tumors in vivo compared to 0% decrease with PMNPs. These results indicate great potential of R11-PMPs as platform technology to target and monitor prostate cancers for diagnostic and therapeutic applications.

RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas.

UNLABELLED: Non-small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Here, we unravel specific requirements for the maintenance of NSCLC that carries this genotype. We establish that the extracellular signal-regulated kinase (ERK)/RHOA/focal adhesion kinase (FAK) network is deregulated in high-grade lung tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice. These findings provide a rationale for the rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer. SIGNIFICANCE: Targeted therapies are effective for only a small fraction of patients with cancer. We report that FAK inhibitors exert potent antitumor effects in NSCLCs that express mutant KRAS in association with INK4A/ARF deficiency. These results reveal a novel genotype-specific vulnerability of cancer cells that can be exploited for therapeutic purposes.