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[EN] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels., The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D.

Chronic lymphocytic leukaemia (CLL) is a malignant B cell disorder characterized by its high heterogeneity. Although genomic alterations have been broadly reported, protein studies are still in their early stages. Herein, a 224-antibody microarray has been employed to study the intracellular signalling pathways in a cohort of 14 newly diagnosed B-CLL patients as a preliminary study for further investigations. Several protein profiles were differentially identified across the cytogenetic and molecular alterations presented in the samples (deletion 13q14 and 17p13.1, trisomy 12, and NOTCH1 mutations) by a combination of affinity and MS/MS proteomics approaches. Among others altered cell signalling pathways, PKC family members were identified as down-regulated in nearly 75% of the samples tested with the antibody arrays. This might explain the rapid progression of the disease when showing p53, Rb1, or NOTCH1 mutations due to PKC-proteins family plays a critical role favouring the slowly progressive indolent behaviour of CLL. Additionally, the antibody microarray results were validated by a LC-MS/MS quantification strategy and compared to a transcriptomic CLL database. In summary, this research displays the usefulness of proteomic strategies to globally evaluate the protein alterations in CLL cells and select the possible biomarkers to be further studied with larger sample sizes., We gratefully acknowledge financial support from the Carlos III Health Institute of Spain (ISCIII, FIS PI11/02114 and FIS PI14/01538), Fondos FEDER (EU), Junta Castilla-Leon SA198A12-2 and BIO/SA03/15. The proteomics analysis was performed in the Proteomics facility of Centro de Investigacion del Cancer (Salamanca, Spain) that belongs to ProteoRed, PRB2- ISCIII, supported by grant PT13/0001. P.D. is supported by a JCYL-EDU/346/2013 PhD scholarship.

Gold–mesoporous silica Janus nanoparticles were prepared through a masking strategy and further employed as building blocks for the preparation of bienzyme biosensors through toposelective immobilization of the corresponding enzymes. The system was evaluated by immobilizing glucose oxidase and horseradish peroxidase on the Au and mesoporous silica faces, respectively. The anisotropic nanoparticles were deposited on glassy carbon electrodes coated with single-walled carbon nanotubes in order to construct an amperometric biosensor for glucose detection. The enzymatic electrode showed excellent electroanalytical performance with a fast response in about 6 s, a linear range of 490 nM–600 μM, a high sensitivity of 4.3 mA M−1 , and a low detection limit of 360 nM for glucose. This biosensor was successfully employed to determine the content of this monosaccharide in commercial soft drink samples.

A novel nanostructured architecture for the construction of electrochemical enzyme biosensors is here described. It implies the electrostatic layer-by-layer assembly of four-generation ethylenediamine core polyamidoamine G-4 dendrimers on glassy carbon electrodes coated with a graphene oxide-carboxymethylcellulose hybrid nanomaterial. This modified surface was further employed for the covalent immobilization of the model enzyme tyrosinase through a glutaraldehyde-mediated cross-linking. The prepared enzyme electrode allowed the amperometric detection of catechol in the 2–400 nM range. The biosensor showed excellent analytical performance with high sensitivity of 6.3 A/M and low detection limit of 0.9 nM. The enzyme electrode retained over 93 % of the initial activity after 40 days at 4 °C.