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Sandra Díez-Villares,1– 3 Juan Pellico,4,5 Noemí Gómez-Lado,6 Santiago Grijalvo,7,8 Sandra Alijas,1 Ramon Eritja,7,8 Fernando Herranz,5,9 Pablo Aguiar,6 María de la Fuente1,2 1Nano-Oncology and Translational Therapeutics group, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, Santiago de Compostela, 15706, Spain; 2Biomedical Research Networking Center on Oncology (CIBERONC), Madrid, 28029, Spain; 3University of Santiago de Compostela (USC), Santiago de Compostela, 15782, Spain; 4School of Biomedical Engineering & Imaging Sciences, King’s College London, St. Thomas’ Hospital, London, SE1 7EH, UK; 5Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, 28029, Spain; 6Nuclear Medicine Department and Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), SERGAS, Santiago de Compostela, 15706, Spain; 7Institute for Advanced Chemistry of Catalonia (IQAC), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, E-08034, Spain; 8Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, 28029, Spain; 9NanoMedMol Group, Instituto de Química Medica (IQM),Consejo Superior de Investigaciones Científicas (CSIC), Madrid, 28006, SpainCorrespondence: María de la FuenteNano-Oncology Unit and Translational Therapeutics Unit, Health Research Institute of Santiago de Compostela (IDIS), Clinical University Hospital (CHUS), Building C, Floor − 2, Lab 18, Travesía da Choupana s/n, Santiago de Compostela, ES15706, SpainTel +34 981 955 704Email maria.de.la.fuente.freire@sergas.esBackground and Purpose: Non-invasive imaging methodologies, especially nuclear imaging techniques, have undergone an extraordinary development over the last years. Interest in the development of innovative tracers has prompted the emergence of new nanomaterials with a focus on nuclear imaging and therapeutical applications. Among others, organic nanoparticles are of the highest interest due to their translational potential related to their biocompatibility and biodegradability. Our group has developed a promising new type of biocompatible nanomaterials, sphingomyelin nanoemulsions (SNs). The aim of this study is to explore the potential of SNs for nuclear imaging applications.Methods: Ready-to-label SNs were prepared by a one-step method using lipid derivative chelators and characterized in terms of their physicochemical properties. Stability was assessed under storage and after incubation with human serum. Chelator-functionalized SNs were radiolabeled with 67Ga and 68Ga, and the radiochemical yield (RCY), radiochemical purity (RCP) and radiochemical stability (RCS) were determined. Finally, the biodistribution of 67/68Ga-SNs was evaluated in vivo and ex vivo.Results: Here, we describe a simple and mild one-step method for fast and efficient radiolabeling of SNs with 68Ga and 67Ga radioisotopes. In vivo experiments showed that 67/68Ga-SNs can efficiently and indistinctly be followed up by PET and SPECT. Additionally, we proved that the biodistribution of the 67/68Ga-SNs can be conveniently modulated by modifying the surface properties of different hydrophilic polymers, and therefore the formulation can be further adapted to the specific requirements of different biomedical applications.Conclusion: This work supports 67/68Ga-SNs as a novel probe for nuclear imaging with tunable biodistribution and with great potential for the future development of nanotheranostics.Keywords: sphingomyelin nanoemulsions, biodistribution, gallium-68/67, nuclear imaging, nanotheranostics

Ghanbar Mahmoodi Chalbatani,1,* Hassan Dana,1,2,* Elahe Gharagouzloo,1 Santiago Grijalvo,3,4 Ramon Eritja,3,4 Craig D Logsdon,5,6 Fereidoon Memari,1 Seyed Rouhollah Miri,1 Mahdi Rezvani Rad,7 Vahid Marmari21Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran; 2Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran; 3Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona 08034, Spain; 4Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER BBN), Madrid, Spain; 5Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA; 6Department of GI Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA; 7Department of Biology, Zabol University, Zabol, Iran*These authors contributed equally to this workAbstract: Cancer is one of the most complex diseases that has resulted in multiple genetic disorders and cellular abnormalities. Globally, cancer is the most common health concern disease that is affecting human beings. Great efforts have been made over the past decades in biology with the aim of searching novel and more efficient tools in therapy. Thus, small interfering RNAs (siRNAs) have been considered one of the most noteworthy developments which are able to regulate gene expression following a process known as RNA interference (RNAi). RNAi is a post-transcriptional mechanism that involves the inhibition of gene expression through promoting cleavage on a specific area of a target messenger RNA (mRNA). This technology has shown promising therapeutic results for a good number of diseases, especially in cancer. However, siRNA therapeutics have to face important drawbacks in therapy including stability and successful siRNA delivery in vivo. In this regard, the development of effective siRNA delivery systems has helped addressing these issues by opening novel therapeutic windows which have allowed to build up important advances in Nanomedicine. In this review, we discuss the progress of siRNA therapy as well as its medical application via nanoparticle-mediated delivery for cancer treatment.Keywords: delivery strategies, lipoplexes, nanovectors, polymeric nanoparticles, siRNA

Noha Attia,1–3,* Mohamed Mashal,1,* Cristina Soto-Sánchez,4,5 Gema Martínez-Navarrete,4,5 Eduardo Fernández,4,5 Santiago Grijalvo,4,6 Ramón Eritja,4,6 Gustavo Puras,1,4 Jose Luis Pedraz1,4,* 1NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; 2Medical Histology and Cell Biology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt; 3Department of Basic Sciences, The American University of Antigua-College of Medicine, Coolidge, Antigua and Barbuda; 4Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; 5Neuroprothesis and Neuroengineering Research Group, Miguel Hernández University, Elche, Spain; 6Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain *These authors contributed equally to this work Background: Gene therapy can be an intriguing therapeutic option in wide-ranging neurological disorders. Though nonviral gene carriers represent a safer delivery system to their viral counterparts, a thorough design of such vehicles is crucial to enhance their transfection properties.Purpose: This study evaluated the effects of combined use of two nonionic surfactants, poloxamer 188 (P) and polysorbate 80 (P80) into nanovesicles – based on 2,3-di(tetradecyloxy)propan-1-amine cationic lipid (D) – destined for gene delivery to central nervous system cells.Methods: Niosome formulations without and with poloxamer 188 (DP80 and DPP80, respectively) were prepared by the reverse-phase evaporation technique and characterized in terms of size, surface charge, and morphology. After the addition of pCMS-EGFP plasmid, the binding efficiency to the niosomes was evaluated in agarose gel electrophoresis assays. Additionally, transfection efficiency of complexes was also evaluated in in vitro and in vivo conditions.Results: In vitro experiments on NT2 cells revealed that the complexes based on a surfactant combination (DPP80) enhanced cellular uptake and viability when compared with the DP80 counterparts. Interestingly, DPP80 complexes showed protein expression in glial cells after administration into the cerebral cortices of rats.Conclusion: These data provide new insights for glia-centered approach for gene therapy of nervous system disorders using cationic nanovesicles, where nonionic surfactants play a pivotal role. Keywords: gene therapy, nonviral gene vectors, poloxamer 188, niosomes, cationic lipids

This article demonstrates a method for the fabrication of patterned surfaces using hairpin oligonucleotides carrying a novel photolabile group at the apex of the loop. Photolysis of surfaces carrying photolabile hairpin oligonucleotides results in the formation of areas carrying single-stranded DNA sequences that direct the deposition of the complementary sequence at the photolysed sites. The non-photolysed areas carrying the intact hairpin do not bind to complementary sequences due to the presence of the more stable intramolecular hairpin duplex. The photolithographic process was performed on silicon wafers and followed by atomic force microscopy and epi-fluorescent microscopy. The method described offers an attractive option for the fabrication of biologically interfaced patterned surfaces with specific recognition properties with potential uses in electronics and as biosensors. [ABSTRACT FROM AUTHOR]

The used tire trade has facilitated the introduction, spread, and establishment of the Asian tiger mosquito, Aedes albopictus, and other mosquito species in several countries of America, Africa, Oceania, and Europe. A strategy for detecting these imported mosquito vectors was developed in Spain during 2003-2004 by EVITAR (multidisciplinary network for the study of viruses transmitted by arthropods and rodents). A survey in 45 locations found no invasive species. Eight autochthonous species of mosquitoes were detected in used tires, including Culex pipiens, Cx. hortensis, Cx. modestus, Anopheles atroparvus, An. claviger, Culiseta longiareolata, Cs. annulata, and Aedes caspius. Dominant species were Cx. pipiens and Cs. longiareolata. Aedes caspius was found in only once, near its natural breeding habitat. Considering the recent discovery of an established population of Ae. albopictus in Catalonia, the increasing commerce of used tires in Spain for recycling, storage, and recapping might greatly contribute to the rapid spread of this species across the Iberian Peninsula. [ABSTRACT FROM AUTHOR]

The synthesis of parallel hairpins carrying 8-aminopurines is described. These hairpins have a high affinity for specific polypyrimidine sequences resulting in the formation of very stable triplexes. [ABSTRACT FROM AUTHOR]

Conjugates of oligonucleotides and alkaline phosphatase have been prepared and used as nonradioactive hybridization probes for the study of Pis3 (=MPI) a gene encoding a proteinase inhibitor from Zea mays. Attachment of the alkaline phosphatase was carried out either at the 5′ or 3′ end of two 25-bp oligonucleotides. Sensitivity of each alkaline phosphatase-oligonucleotide probe was assessed using a chemiluminescent substrate for detection of alkaline phosphatase activity. This sensitive method allows the rapid analysis of genomic clones isolated from a Zea mays library and the subsequent characterization of the complete Pis3 gene without the need for construction of restriction maps for the cloned DNA fragments. This general strategy may be valuable for the identification of any gene for which a limited sequence is known and for location of specific DNA sequences that represent a small region within a larger DNA fragment. [ABSTRACT FROM AUTHOR]

The mutagenic potential of -methylthymine (mT) and -ethylthymine (eT) was determined by a primer extension assay on a 25mer oligonucleotide containing a single sitespecifically incorporated modified thymine. The eT-containing oligonucleotide was prepared by using a new synthetic procedure suitable for large alkyl groups on thymine. The second-order rate constants, K and V, permitted calculation of the frequency of formation and extension of modified base pairs compared to Watson — Crick pairing. With both mT and eT, the T.G type pairing was formed at least 10-fold more frequently than the non-mutagenic alkyl T.A pairing. However, there was a small but reproducible preference for mT.G pairing. In both cases T ↑ C transitions would result. There was no evidence for formation of alkyl T.C or T.T. These data suggest that reported T — A transversions by ethylation are not likely to result from -alkylthymine. In contrast to insertion, extension beyond alkylthymine under kinetic conditions did not occur with alkyl T.A but only with the alkyl T-G termini. For this latter T-G type pairing, the larger ethyl group did not hinder extension compared to that of the methyl group, in the sequence studied. Under non-limiting conditions of dNTP concentration and time, complete replication could be demonstrated for both methyl- and ethyl-containing oligonucleotides. We conclude that the increase in size of the alkyl group from methyl to ethyl does not significantly affect the mutagenic potential and type of mutations of -alkylthymine . [ABSTRACT FROM PUBLISHER]

A correction to an author's affiliation published in a previous issue is presented.