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Aim: We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Materials & methods: Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice. Results: Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro. Conclusion: TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy. Original submitted 6 November 2012; Revised submitted 25 March 2013

Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously—fluorescence optical imaging and magnetic resonance imaging—with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell-based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe 3 O 4 and the fluorophore ICG, which results in a high T 2 relaxivity (390mm ―1 s ―1 ) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near-IR illumination.

Six different eupomatenoids ( 1a–c , 1f–h ) were prepared from 2,3,5-tribromobenzofuran ( 2 ) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high regioselectivity achieved in three Pd(0)- and Ni(0)-catalyzed cross-coupling reactions which were conducted consecutively. The order of substitution at the benzofuran nucleus is C-2, C-5 and C-3.

We investigate reflectance mode multi-frequency domain optical imaging with novel theranostic silica core gold nanostructures with Indocyanine Green. From phase sensitive images from homodyne measurements we determine optimal measurement parameters for nanoshell enhanced fluorescent dyes.

Multimodality molecular imaging is becoming more and more important to understand both the structural and the functional characteristics of tissue, organs and tumors. So far, invasive nuclear methods utilizing ionizing radiation have been the “gold standard” of molecular imaging. We investigate non-contact, non-invasive, patient-tolerant and inexpensive near infrared (NIR) frequency domain optical tomography (FDOT) as a functional complement to structural X-ray computed tomography (CT) data. We show a novel multifrequency NIR FDOT approach both in transmission and reflectance mode and employ radiative transport equation (RTE) for 3D reconstruction of a target with novel fluorescent gold nanoshell indocyanine green (NS ICG) in an ex vivo nude mouse. The results demonstrate that gold NS ICG with multifrequency NIR FDOT is a promising fluorophore for multimodal optical molecular image reconstruction.

Thirty-five novel substituted imidazolyl methylene biphenyls have been synthesized as CYP17 inhibitors for the potential treatment of prostate cancer. Their activities have been tested with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against CYP11B1, CYP11B2, and hepatic CYP enzymes 3A4, 1A2, 2B6 and 2D6. The core rigidified compounds (30-35) were the most active ones, being much more potent than Ketoconazole and reaching the activity of Abiraterone. However, they were not very selective. Another rather potent and more selective inhibitor (compound 23, IC(50)=345 nM) was further examined in rats regarding plasma testosterone levels and pharmacokinetic properties. Compared to the reference Abiraterone, 23 was more active in vivo, showed a longer plasma half-life (10h) and a higher bioavailability. Using our CYP17 homology protein model, docking studies with selected compounds were performed to study possible interactions between inhibitors and amino acid residues of the active site.

Six different eupomatenoids ( 1a–c , 1f–h ) were prepared from 2,3,5-tribromobenzofuran ( 2 ) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high regioselectivity achieved in three Pd(0)- and Ni(0)-catalyzed cross-coupling reactions which were conducted consecutively. The order of substitution at the benzofuran nucleus is C-2, C-5 and C-3.