ysk05 and Kidney-Neoplasms

ysk05 has been researched along with Kidney-Neoplasms* in 2 studies

Reviews

1 review(s) available for ysk05 and Kidney-Neoplasms

ArticleYear
[Development of siRNA Delivery Targeting the Tumor Microenvironment with a New Functional Device].
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2019, Volume: 139, Issue:11

    The tumor microenvironment plays a key role in cancer progression, drug resistance, metastasis, etc. To establish a new therapeutic strategy based on control of the tumor microenvironment, I have developed a lipid nanoparticle (LNP)-based in vivo small interfering RNA (siRNA) delivery system equipped with a targeting ligand. First, I established an LNP that induces membrane fusion in response to acidification after internalization by cells using the original pH-sensitive cationic lipid YSK05. A modification of polyethylene glycol to YSK05-containing LNPs allowed significant gene silencing in the human renal cell carcinoma model. Then, I attempted to establish a tumor vasculature-targeting LNP because the vasculature is responsible for the tumor microenvironment. Cyclic RGD peptide is known to be a ligand against integrin αVβ3, which is highly expressed on tumor endothelial cells (TECs). Optimized cyclic RGD peptide-modified LNP (RGD-LNP) suppressed gene expression in TECs to 50%. The inhibition of vascular endothelial cell growth factor receptor 2 (VEGFR2), which is a dominant factor in angiogenesis, by the injection of RGD-LNP significantly delayed tumor growth. Finally, I examined the effect of RGD-LNP on the tumor microenvironment. The suppression of VEGFR2 increased pericyte coverage and endothelial junctions, which indicate maturation of the vasculature. In RGD-LNP-treated mice, systemically administered nanoparticles encapsulating doxorubicin were distributed in a larger area than in untreated mice. Moreover, the therapeutic effect of doxorubicin-loaded liposomes was significantly enhanced by RGD-LNP. In conclusion, I succeeded in developing a new therapy based on regulation of the tumor microenvironment.

    Topics: Angiogenesis Inhibitors; Animals; Carcinoma, Renal Cell; Doxorubicin; Drug Delivery Systems; Gene Silencing; Humans; Hydrogen-Ion Concentration; Kidney Neoplasms; Lipids; Mice; Molecular Targeted Therapy; Nanoparticles; Piperidines; RNA, Small Interfering; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2

2019

Other Studies

1 other study(ies) available for ysk05 and Kidney-Neoplasms

ArticleYear
Modality of tumor endothelial VEGFR2 silencing-mediated improvement in intratumoral distribution of lipid nanoparticles.
    Journal of controlled release : official journal of the Controlled Release Society, 2017, 04-10, Volume: 251

    The vascular endothelial growth factor (VEGF)-mediated enhancement in vascular permeability is considered to be a major factor in tumor-targeting delivery via the enhanced permeability and retention (EPR) effect. We previously reported that the silencing of the endothelial VEGF receptor (VEGFR2) by a liposomal siRNA system (RGD-MEND) resulted in an enhanced intratumoral distribution of polyethylene glycol (PEG)-modified liposomes (LPs) in a renal cell carcinoma, a type of hypervascularized cancer, although the inhibition of VEGF signaling would be expected to decrease the permeability of the tumor vasculature. We herein report that the enhancement in the intratumoral distribution of LPs by VEGFR2 inhibition was dependent on the vascular type of the tumor (stroma vessel type; SV and tumor vessel type; TV). In the case of TV-type tumors (renal cell carcinoma and hepatocellular carcinoma), inhibiting VEGFR2 improved intratumoral distribution, while no effect was found in the case of SV-type tumors (colorectal cancer). Moreover, through a comparison of the intratumoral distribution of LPs with a variety of physical properties (100nm vs 400nm, neutral vs negative vs positive), VEGFR2 inhibition was found to alter the tumor microenvironment, including heparan sulfate proteoglycans (HSPGs). In addition, the results regarding the effect of the size of nanoparticles indicated that VEGFR2 inhibition improved the penetration of nanoparticles through the vessel wall, but not via permeability, suggesting the involvement of an unknown mechanism. Our findings suggest that a combination of anti-angiogenic therapy and delivery via the EPR effect would be useful in certain cases, and that altering the tumor microenvironment by VEGFR2 blockade has a drastic effect on the intratumoral distribution of nanoparticles.

    Topics: Animals; Antineoplastic Agents; Capillary Permeability; Carcinoma, Renal Cell; Cell Line, Tumor; Female; Humans; Kidney Neoplasms; Lipids; Liposomes; Male; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, Nude; Nanoparticles; Oligopeptides; Particle Size; Piperidines; Polyethylene Glycols; RNA, Small Interfering; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2

2017