{"title":"Comparative Activity and Specificity of Antisense Oligodeoxynucleotides and Small Interfering RNA in an in vitro Ewing Sarcoma Model","authors":"M. Villemeur, A. Tamaddon, J. Bertrand, C. Malvy","doi":"10.2174/1875933500902010036","DOIUrl":"https://doi.org/10.2174/1875933500902010036","url":null,"abstract":"The EWS-Fli1 fusion gene, resulting from a t(11;22) translocation, plays a key role in the Ewing's sarcoma pathogenesis. In the past, a 25mer phosphorothioate antisense oligodeoxynucleotide, a structured 30mer phos- phorothioate/phosphodiester antisense oligodeoxynucleotide, and an antisense siRNA, delivered either free, by vectors or intracellularly expressed, were found potent in various in vitro and in vivo Ewing sarcoma models. Because of differences among the models used in the literature, the comparison of various antisense agents with each other is difficult. Therefore, we aimed to evaluate these three antisense agents in NIH/3T3 fibroblasts which stably express the human EWS-Fli1 on- cogene as an in vitro model of Ewing sarcoma. Fours parameters were considered including oncogene EWS-Fli1 and EWS mRNA expression, cellular proliferation, and actin cytoskeleton organization. They illustrate the antisense efficacy, the specificity and the phenotypic reversion for the last two ones, respectively. We showed that the structured 30mer phosphorothioate/phosphodiester antisense oligodeoxynucleotide and antisense siRNA represent the best choice for clini- cal trials. Nevertheless, the antisense ODN is more specific than the siRNA and represents the most efficient antisense agent. Its activity may be improved after the selection of an appropriate delivery vector which is able to increase cell penetration and to protect it from nucleases degradation.","PeriodicalId":22993,"journal":{"name":"The Open Nanomedicine Journal","volume":"8 1","pages":"36-45"},"PeriodicalIF":0.0,"publicationDate":"2009-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81719240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Raman, G. Machaidze, A. Lustig, V. Olivieri, U. Aebi, P. Burkhard
{"title":"Design of Peptide Nanoparticles Using Simple Protein Oligomerization Domains","authors":"S. Raman, G. Machaidze, A. Lustig, V. Olivieri, U. Aebi, P. Burkhard","doi":"10.2174/1875933500902010015","DOIUrl":"https://doi.org/10.2174/1875933500902010015","url":null,"abstract":"Viruses are naturally formed bionanoparticles ranging in size from about 20 to 150 nm. Remarkably, small vi- ruses are composed of one single protein chain folding into a capsid structure with icosahedral symmetry. The icosahe- dron is built from 60 asymmetric units and is the largest closed shell in which every subunit is in an identical environ- ment. It is characterized by 2-fold, 3-fold and 5-fold rotational symmetry axes. By superposition of different protein oli- gomerization domains onto the symmetry axes of an icosahedron, a nanoparticle with icosahedral symmetry can be de- signed. We have recently described such a design of peptide nanoparticles using coiled-coil protein oligomerization do- mains. Here we show that oligomerization motifs other than coiled-coils can be used to form nanoparticles by incorporat- ing the globular foldon domain from fibritin with a trimeric -sheet conformation into the design. We expressed and puri- fied 8 different peptides and performed refolding studies and biophysical characterization with analytical ultra centrifuga- tion (AUC) and electron microscopy (EM). In the first design version we joined the foldon domain to the pentameric coiled-coil domain of COMP and varied the lengths of the linker sequences between the two domains. In this design we observed only smaller nanoparticles. When in the second design the foldon domain was extended with an additional trimeric coiled-coil domain as a combined trimerization domain that is linked to the COMP pentamer, we observed nanoparticles of sizes and molecular weights as would be expected for icosahedral symmetry. Viruses and virus-like parti- cles (VLPs) are known for their ability to induce a strong humoral and hence antibody mediated immune response due to their repetitive antigen display. Peptide based nanoparticles have similar properties to VLPs, which are in clinical trials as a carrier in vaccination. Therefore, these peptide nanoparticles represent an alternative platform for subunit vaccine using the concept of repetitive antigen display.","PeriodicalId":22993,"journal":{"name":"The Open Nanomedicine Journal","volume":"14 1","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"2009-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87940206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Opto-Mechanical Manipulation of Stem Cells","authors":"Hu Zhang, Kuo-Kang Liu, A. E. Haj","doi":"10.2174/1875933500902010010","DOIUrl":"https://doi.org/10.2174/1875933500902010010","url":null,"abstract":"Stem cells have a great potential for regeneration of injured or degenerated tissues or organs. In delivery of cell therapy, stem cells are normally subjected to different levels of shear stress which may have a great impact on their prolif- eration and differentiation after they reach the target site. Although the shear stress has been recognized as one of key fac- tors, the study on how it affects single stem cell mechanobiologically is not available. This paper reports an application of optical tweezers for manipulating the human mesenchymal stem cells which are exposed to various levels of shear stress in flow chambers. Our preliminary results show different responses of stem cells (the tether formation, cell shrinkage, presence of cell surface nanoparticles, cell rotation before aligning the flow direction) under shear forces in different flow chambers. Also, a few interesting optical characteristics of stem cells have been noticed; for example, the variation of re- fractive index within the cell may lead to different behaviors when they are manipulated by optical tweezers.","PeriodicalId":22993,"journal":{"name":"The Open Nanomedicine Journal","volume":"91 1","pages":"10-14"},"PeriodicalIF":0.0,"publicationDate":"2009-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85662358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaibhav Saini, Dmitri V Martyshki, Victoria D Towner, Sergey B Mirov, Maaike Everts
{"title":"Limitations of Adenoviral Vector-Mediated Delivery of Gold Nanoparticles to Tumors for Hyperthermia Induction.","authors":"Vaibhav Saini, Dmitri V Martyshki, Victoria D Towner, Sergey B Mirov, Maaike Everts","doi":"10.2174/1875933500902010027","DOIUrl":"https://doi.org/10.2174/1875933500902010027","url":null,"abstract":"<p><p>Novel combinatorial treatment strategies are desired to achieve tumor eradication. In this regard, nanotechnology and gene therapy hold the potential to expand the available tumor treatment options. In particular, gold nanoparticles (AuNPs) have been utilized for hyperthermic tumor cell ablation. Similarly, adenoviral (Ad) vectors have been utilized for targeting, imaging, and cancer gene therapy. Thus, to combine AuNP-mediated hyperthermia with Ad vector-based gene therapy, we have previously coupled AuNPs to Ad vectors. Herein we tested the capability of these AuNP-coupled Ad vectors for hyperthermic tumor cell ablation. Towards this end, we compared absorption characteristics of different sized AuNPs and determined that in our system 20 nm diameter AuNPs are suitable for laser induced hyperthermic tumor cell killing. In addition, we observed that AuNPs outside and inside the cell contribute differentially towards hyperthermia induction. Unfortunately, due to the limitation of delivery of required amounts of AuNPs to cells, we observed that AuNP-coupled Ad vectors are unable to kill tumor cells via hyperthermia. However, with future technological advances, it may become possible to realize the potential of the multifunctional AuNP-coupled Ad vector system for simultaneous targeting, imaging, and combined hyperthermia and gene therapy of tumors.</p>","PeriodicalId":22993,"journal":{"name":"The Open Nanomedicine Journal","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882004/pdf/nihms-539477.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32011971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Khaled, B. Abu-Sharkh, A. Khalil, A. Manda, E. Amr
{"title":"Novel Antimicrobial Polyelectrolytes Nanofilm Coatings Using the Layer By Layer Technique","authors":"M. Khaled, B. Abu-Sharkh, A. Khalil, A. Manda, E. Amr","doi":"10.2174/1875933500801010001","DOIUrl":"https://doi.org/10.2174/1875933500801010001","url":null,"abstract":"A novel method using the layer by layer (LBL) technique was investigated to deposit polyelectrolytes with an- tibacterial properties. A glass substrate was coated by a cationic biguanide followed by the anionic polystyrene sulfonate until a total of twenty layers were deposited. The layers thickness was measured by ellipsometry and the surface morphol- ogy was scanned by an atomic force microscope. The layers thickness reached 60nm. The coated and uncoated glass was immersed into tubes containing a nutrient broth media inoculated with Proteus sp., (a gram negative , rod, glucose fer- menting bacteria) in a concentration of (~10 5 cells/mL) and incubated at 37°C for 24 hours. The SEM (Scanning Electron Microscope) micrographs showed a significant reduction in the settlement of Proteus sp. Colonies on the glass coated with polyelectrolytes.","PeriodicalId":22993,"journal":{"name":"The Open Nanomedicine Journal","volume":"36 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2008-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90755883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}