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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