ysk05 has been researched along with Neoplasms* in 6 studies
1 review(s) available for ysk05 and Neoplasms
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[Development of an efficient short interference RNA (siRNA) delivery system with a new pH-sensitive cationic lipid].
The development of a carrier for the delivery of siRNA is a factor in the realization of RNA interference (RNAi) therapeutics. Modification of siRNA carriers with polyethylene glycol, i.e., PEGylation, is a general strategy for stabilizing a particle in the blood stream and delivering it to tissue or cells. However, it is well-known that, when a carrier is modified by PEGylation, it results in a significant inhibition of both cellular uptake and the endosomal escape process. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for delivering siRNA and peptide-based functional devices for overcoming the effects conferred by PEGylation and succeeded in the delivery of siRNA to tumor tissue. In this study, we noticed that the pH-sensitive property, changing from neutral to cationic in response to a decrease in pH, could avoid the inhibition caused by PEGylation and succeeded in synthesizing a pH-sensitive cationic lipid, YSK05. The YSK05-MEND had a higher fusogenicity and potency for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and avoided the inhibition of endosomal escape caused by PEGylation followed by optimization of the lipid composition. Furthermore, the intratumoral injection of the PEGylated YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Thus, the YSK05-MEND is a promising siRNA carrier for avoiding the inhibition in intracellular trafficking caused by PEGylation both in vitro and in vivo. Topics: Animals; Cations; Drug Delivery Systems; Drug Discovery; Endosomes; Gene Silencing; Humans; Hydrogen-Ion Concentration; Injections, Intralesional; Lipids; Nanostructures; Neoplasms; Piperidines; Polyethylene Glycols; RNA, Small Interfering | 2012 |
5 other study(ies) available for ysk05 and Neoplasms
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Spleen selective enhancement of transfection activities of plasmid DNA driven by octaarginine and an ionizable lipid and its implications for cancer immunization.
Efficiently delivering plasmid DNA (pDNA) to the spleen is particularly significant for DNA immunization. However, increasing the efficiency of gene expression in spleen cells for achieving a therapeutic effect remains a serious challenge. An ideal spleen-targeted system should avoid liver uptake and should efficiently transfect specific functional spleen cells. Here, we report on pDNA nanocarriers with enhanced transfection in spleen cells driven by synergism between an octaarginine (R8) peptide and YSK05; a pH-responsive ionizable lipid. A double-coating design is essential for enhancing spleen selective transfection which is significantly affected by the total amount of lipid and the composition of the outer coat. The optimized R8/YSK system shows a high gene expression in the spleen with a high spleen/liver ratio and a surprising ability to target spleen B cells. Compared to other organs, the high spleen activity cannot be explained based on the amount of pDNA delivered to each organ, indicating that the system is extremely efficient in transfecting spleen cells. The system can be used in cancer immunization where a strong anti-tumor effect was observed in mice immunized with the R8/YSK system encapsulating antigen-encoding pDNA. The R8/YSK system holds great promise for future applications in the field of DNA vaccination. Topics: Animals; B-Lymphocytes; DNA; Female; Gene Transfer Techniques; Humans; Hydrogen-Ion Concentration; Immunization; Lipids; Liver; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Nanocapsules; Neoplasms; Oligopeptides; Piperidines; Plasmids; Spleen; Transfection | 2019 |
RNAi-mediated gene knockdown and anti-angiogenic therapy of RCCs using a cyclic RGD-modified liposomal-siRNA system.
Angiogenesis is one of crucial processes associated with tumor growth and development, and consequently a prime target for cancer therapy. Although tumor endothelial cells (TECs) play a key role in pathological angiogenesis, investigating phenotypical changes in neovessels when a gene expression in TEC is suppressed is a difficult task. Small interfering RNA (siRNA) represents a potential agent due to its ability to silence a gene of interest. We previously developed a system for in vivo siRNA delivery to cancer cells that involves a liposomal-delivery system, a MEND that contains a unique pH-sensitive cationic lipid, YSK05 (YSK-MEND). In the present study, we report on the development of a system that permits the delivery of siRNA to TECs by combining the YSK-MEND and a ligand that is specific to TECs. Cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) is a well-known ligand to αVβ3 integrin, which is selectively expressed at high levels in TECs. We incorporated cRGD into the YSK-MEND (RGD-MEND) to achieve an efficient gene silencing in TECs. Quantitative RT-PCR and the 5' rapid amplification of cDNA ends PCR indicated that the intravenous injection of RGD-MEND at a dose of 4.0mg/kg induced a significant RNAi-mediated gene reduction in TEC but not in endothelial cells of other organs. Finally, we evaluated the therapeutic potency of the RGD-MEND encapsulating siRNA against vascular endothelial growth factor receptor 2. A substantial delay in tumor growth was observed after three sequential RGD-MEND injections on alternate days. In conclusion, the RGD-MEND represents a new approach for the characterization of TECs and for us in anti-angiogenic therapy. Topics: Animals; Drug Delivery Systems; HEK293 Cells; Human Umbilical Vein Endothelial Cells; Humans; Lipids; Liposomes; Male; Mice; Mice, Inbred BALB C; Neoplasms; Neovascularization, Pathologic; Peptides, Cyclic; Piperidines; RNA Interference; RNA, Small Interfering; Vascular Endothelial Growth Factor Receptor-2 | 2014 |
A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer immunotherapy.
Cyclic dinucleotides are of importance in the field of microbiology and immunology. They function as second messengers and are thought to participate in the signal transduction of cytosolic DNA immune responses. One such dinucleotide, cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons. Therefore c-di-GMP can be thought of as a new class of adjuvant. However, because c-di-GMP contains two phosphate groups, this prevents its use as an adjuvant because it cannot pass through the cell membrane, even though the target molecule of c-di-GMP is located in the cytoplasm. Our group has been developing a series of liposomal drug delivery systems and recently investigated YSK05 which is a synthetic, pH sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN-β in Raw264.7 cells. The induction of IFN-β from c-di-GMP liposomes was inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of IFN-β caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I. The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell activity and the inhibition of tumor growth in a mouse model. These findings indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di-GMP to the cytosol and induce an innate immune system but also as a platform for investigating the mechanism of immune sensing with cyclic dinucleotides in vitro and in vivo. Topics: Adjuvants, Immunologic; Animals; Cancer Vaccines; Cell Line; Cell Line, Tumor; Cyclic GMP; Female; Immunotherapy; Interferon-beta; Lipids; Liposomes; Mice, Inbred C57BL; Neoplasms; Ovalbumin; Piperidines; T-Lymphocytes, Cytotoxic; Tumor Burden | 2014 |
Gene silencing via RNAi and siRNA quantification in tumor tissue using MEND, a liposomal siRNA delivery system.
Small interfering RNA (siRNA) would be predicted to function as a cancer drug, but an efficient siRNA delivery system is required for clinical development. To address this issue, we developed a liposomal siRNA carrier, a multifunctional envelope-type nanodevice (MEND). We previously reported that a MEND composed of a pH-sensitive cationic lipid, YSK05, showed significant knockdown in both in vitro and in tumor tissue by intratumoral injection. Here, we report on the development of an in vivo siRNA delivery system that is delivered by systemic injection and an analysis of the pharmacokinetics of an intravenously administered siRNA molecule in tumor tissue. Tumor delivery of siRNA was quantified by means of stem-loop primer quantitative reverse transcriptase PCR (qRT-PCR) method. PEGylation of the YSK-MEND results in the increase in the accumulation of siRNA in tumor tissue from 0.0079% ID/g tumor to 1.9% ID/g tumor. The Administration of the MEND (3 mg siRNA/kg body weight) showed about a 50% reduction in the target gene mRNA and protein. Moreover, we verified the induction of RNA interference by 5' RACE-PCR method. The collective results reported here indicate that an siRNA carrier was developed that can deliver siRNA to a target cell in tumor tissue through an improved siRNA bioavailability. Topics: Administration, Intravenous; Amino Acid Sequence; Animals; Cell Line, Tumor; Gene Transfer Techniques; Humans; Lipids; Liposomes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Microscopy, Confocal; Molecular Sequence Data; Neoplasms; Piperidines; Polyethylene Glycols; RNA Interference; RNA, Messenger; RNA, Small Interfering; Toxicity Tests | 2013 |
A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo.
Modification of liposomal siRNA carriers with polyethylene glycol, i.e., PEGylation, is a generally accepted strategy for achieving in vivo stability and delivery to tumor tissue. However, PEGylation significantly inhibits both cellular uptake and the endosomal escape process of the carriers. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for siRNA delivery and peptide-based functional devices for overcoming the limitations and succeeded in the efficient delivery of siRNA to tumors. In this study, we synthesized a pH-sensitive cationic lipid, YSK05, to overcome the limitations. The YSK05-MEND had a higher ability for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and overcame the limitations followed by optimization of the lipid composition. Furthermore, the intratumoral administration of the YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Collectively, these data confirm that YSK05 facilitates the endosomal escape of the MEND and thereby enhances the efficacy of siRNA delivery into cytosol and gene silencing. Topics: Animals; Cell Cycle Proteins; Cell Line, Tumor; Endocytosis; Erythrocytes; Gene Silencing; HeLa Cells; Humans; Hydrogen-Ion Concentration; Lipids; Liposomes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Nanostructures; Neoplasms; Peptides; Piperidines; Polo-Like Kinase 1; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; RNA, Small Interfering | 2012 |