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A supramolecular approach has been developed for the preparation of supramolecular nanoparticles (SNPs) with variable sizes (30-450 nm) from three different molecular building blocks using a cyclodextrin/adamantane recognition system. Positron emission tomography (PET) was employed to study the biodistribution and lymph node drainage of the SNPs in mice. The sizes of the SNPs affect their in vivo characteristics (see picture).

The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform, Microfluidic Image Cytometry (MIC), capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000-2,800 cells. Using cultured cell lines, we demonstrate simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt and phospho-S6) within the oncogenic PI3K/Akt/mTOR signaling pathway. To demonstrate the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking inter- and intra-tumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters which predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine.

Abstract. The aim of this study was to assess the significance of expression of hypoxia-inducible factor-1α (HIF-1α) and associated proteins in pancreatic ductal adenocarcinoma (PDA) and their impact on prognosis. Expression of HIF-1α, vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), survivin, CD34 and Ki-67 and apoptotic cells was demonstrated by immunohistochemistry or TUNEL in 58 PDAs and 20 normal pancreatic tissue samples. Our results show positivity of HIF-1α, VEGF, Glut-1 and survivin in 70.7%, 77.6%, 67.2% and 84.5% of the patients with PDA, respectively, which is significantly higher than in the normal counterparts. Expression of HIF-1α correlated positively with VEGF and Glut-1 expression but not with survivin. Strong HIF-1α expression associated with decreased apoptotic index and increased intratumoral microvessel density. Higher HIF-1α, VEGF and Glut-1 expression significantly associated with advanced tumor stage and lymph node metastasis. Patients with high HIF-1α, VEGF and Glut-1 expressing tumors had a poorer overall survival. Furthermore, Cox regression analysis showed that HIF-1α is a prognostic marker of borderline significance while VEGF was important in predicting poor outcome. These results suggest that over-expression of HIF-1α may play an important role in cancer progression through upregulation of VEGF and Glut-1 in PDA patients. HIF-1α and VEGF are potential candidates for predicting survival.

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Aus drei Bausteinen entstehen auf der Grundlage eines Cyclodextrin‐Adamantan‐Erkennungssystems supramolekulare Nanopartikel (SNPs) variabler Größe (30–450 nm). Die Bioverteilung und Lymphknotendrainage der SNPs in Mäusen wurde mit Positronenemissionstomographie untersucht. Die Größen der SNPs beeinflussen ihr In‐vivo‐Verhalten (siehe Bild).

We demonstrated a convenient, flexible and modular synthetic approach for preparation of a small library of DNA encapsulated supramolecular nanoparticles SNPs⊃DNA and RGD-SNPs⊃DNA with different sizes and RGD target ligand coverage for targeted gene delivery.

The direct ethanol fuel cells in an alkaline medium have a broad vision of applications because of their large energy density, reasonable power density, and environmentally friendly features. Herein, we present a facile one-step method to synthesize PdAg nanosheet assemblies (NSAs) in a mixed solution of N,Ndimethylformamide and water with the addition of molybdenum hexacarbonyl and cetyltrimethylammonium bromide. Pure Pd NSA shows an irregular shape while PdAg NSAs gradually undergo a process from solid assembly to a hollow structure with the Pd/Ag molar ratio changing from 3:1 to 2:1 to 1:1. The formation of alloy nanosheets in the assemblies combined with the introduction of Ag in the Pd catalyst enhances the catalytic activity toward ethanol electrooxidation from 1524 mA mg −1 of pure Pd NSA to 1866 mA mg −1 of PdAg NSA with a Pd/Ag molar ratio of 2:1. On the basis of the experimental data, compared with pure Pd structures, both the nature of a thin nanosheet of PdAg NSAs and the structural changes in the alloy assemblies play key roles in determining the electrocatalytic activity of these Pd-based catalysts.