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Redox-triggered intracellular siRNA delivery
Chem. Commun., 2018, Accepted Manuscript DOI: 10.1039/C8CC01376D, CommunicationNecibe Basaran Mutlu Agardan, Can Sarisozen, Vladimir Torchilin Stimuli-responsive nanopreparations are able to provide drug release in response to various physiological stimuli including redox potential. Gene silencing using small interfering RNA (siRNA) is a promising strategy for the... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - May 29, 2018 Category: Chemistry Authors: Necibe Basaran Mutlu Agardan Source Type: research
Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma.
In this study, we assembled lipid/calcium/phosphate nanoparticles (LCP NPs) conjugated with eight types of galactoside derivatives and demonstrated that phenyl β-d-galactoside-decorated LCP NPs (L4-LCP NPs) exhibited a superior siRNA delivery into HCC cells compared to normal hepatocytes. VEGF siRNAs delivered by L4-LCP NPs downregulated VEGF expression in HCC in vitro and in vivo and led to a potent antiangiogenic effect in the tumor microenvironment of a murine orthotopic HCC model. The efficient delivery of VEGF siRNA by L4-LCP NPs that resulted in significant tumor regression indicates that phenyl galactoside could be...
Source: Biomacromolecules - May 29, 2018 Category: Biochemistry Authors: Huang KW, Lai YT, Chern GJ, Huang SF, Tsai CL, Sung YC, Chiang CC, Hwang PB, Ho TL, Huang RL, Shiue TY, Chen Y, Wang SK Tags: Biomacromolecules Source Type: research
The study of relationships between pKa value and siRNA delivery efficiency based on tri-block copolymers.
Abstract Tri-block copolymers have exhibited great potentials in small interfering RNA (siRNA) therapeutics. To reveal structure-activity relationships, we here synthesized a series of tri-block copolymers with different hydrophobic segments, PEG-PAMA-P(C6Ax-C7Ay-DPAz-DBAm) (EAAS) and PEG-PDAMAEMA-P(C6Ax-C7Ay-DPAz-DBAm) (EDAS), termed from EAASa to EAASh and EDASa to EDASh, with pKa ranging from 5.2 to 7.0. Our data showed that the better gene silencing efficiency was located in pKa of 5.8-6.2, which was contributed from higher endosomal escape observed with confocal images and hemolysis assay. EAASc, the leader p...
Source: Biomaterials - May 29, 2018 Category: Materials Science Authors: Du L, Wang C, Meng L, Cheng Q, Zhou J, Wang X, Zhao D, Zhang J, Deng L, Liang Z, Dong A, Cao H Tags: Biomaterials Source Type: research
Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin Nanocapsules
Publication date: Available online 26 May 2018 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya Xiang Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - May 27, 2018 Category: Nanotechnology Source Type: research
Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy
Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Jun Li, Huamin Liang, Jing Liu, Ziyuan Wang Poly (amidoamine) (PAMAM) dendrimers are well-defined, highly branched macromolecules with numerous active amine groups on the surface. Because of their unique properties, PAMAM dendrimers have steadily grown in popularity in drug delivery, gene therapy, medical imaging and diagnostic application. This review focuses on the recent developments on the application in PAMAM dendrimers as effective carriers for drug and gene (pDNA, siRNA) delivery in cancer therapy, incl...
Source: International Journal of Pharmaceutics - May 26, 2018 Category: Drugs & Pharmacology Source Type: research
Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin Nanocapsules
Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice. NPC/Bmi1siR was fabricated via electrostatic complexation of Bmi1 siRNA to NPCs, which had cores composed of cisplatin and were coated with cationic lipids.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - May 26, 2018 Category: Nanotechnology Authors: Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya Xiang Source Type: research
AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1
In conclusion, AMF siRNA is expected to be a novel strategy to treat KD by inhibiting signaling pathway of RhoA/ROCK1.
Source: Genes and Diseases - May 19, 2018 Category: Genetics & Stem Cells Source Type: research
Molecular therapy using siRNA: Recent trends and advances of multi target inhibition of cancer growth.
Abstract RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy. Furthermore, a combination of ...
Source: International Journal of Biological Macromolecules - May 18, 2018 Category: Biochemistry Authors: Jain S, Pathak K, Vaidya A Tags: Int J Biol Macromol Source Type: research
GSE100403 A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis
Contributors : Simona Pavan ; Nathalie Meyer-Schaller ; Ravi K Kalathur ; Meera Saxena ; Gerhard ChristoforiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe have employed a high-content microscopy screen in combination with a kinome and phosphatome-wide siRNA library to identify signaling pathways underlying an EMT of murine mammary epithelial cells and breast cancer cells. This screen identified the MEK5-ERK5 axis as a critical player in TGFb-mediated EMT. Suppression of MEK5-ERK5 signaling completely prevented the morphological and molecular changes occurring during a TGFb-induced...
Source: GEO: Gene Expression Omnibus - May 17, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Efficient siRNA transfer to knockdown a placenta specific lncRNA using RGD-modified nano-liposome: A new preeclampsia-like mouse model
Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Qianwen Yu, Yue Qiu, Xuhui Wang, Jiajing Tang, Yayuan Liu, Ling Mei, Man Li, Ming Yang, Li Tang, Huile Gao, Zhirong Zhang, Wenming Xu, Qin He Preeclampsia is one of the most serious pregnancy complications. Many animal models have already been developed by researchers to study the pathogenesis and treatment of preeclampsia. However, most of these animal models were established by systemic administration or by surgery in the uterine cavity, which could lead to unwanted systemic toxicity or operative wounds and ...
Source: International Journal of Pharmaceutics - May 17, 2018 Category: Drugs & Pharmacology Source Type: research
Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer
In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results als...
Source: Molecular Immunology - May 17, 2018 Category: Allergy & Immunology Source Type: research
Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-loaded Polyion Complex Micelle for Optimizing Targetability into Pancreatic Cancer Cells.
Abstract Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) (PEG) and poly(L-lysine) (PLL), and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified anti-human tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic (FCS) analysis revealed that 1, 2, or 3 molecule(s) of Fab'(s) were installed onto one micellar ...
Source: Biomacromolecules - May 16, 2018 Category: Biochemistry Authors: Min HS, Kim HJ, Ahn J, Naito M, Hayashi K, Toh K, Kim BS, Matsumura Y, Kwon IC, Miyata K, Kataoka K Tags: Biomacromolecules Source Type: research
TRIM24 siRNA induced cell apoptosis and reduced cell viability in human nasopharyngeal carcinoma cells.
Authors: Wang P, Shen N, Liu D, Ning X, Wu D, Huang X Abstract Nasopharyngeal carcinoma (NPC) is a common cancer occurring primarily in East Asia and Africa. The high rate of recurrence and metastasis of NPC continuously endangers the health of patients. The present study aimed to identify the underlying mechanisms involved in the progression of NPC and provide experimental basis to develop a novel and efficient agent against NPC. The present study measured the expression level of tripartite motif containing 24 (TRIM24) in tumor tissues from NPC patients using reverse transcription quantitative polymerase chain re...
Source: Molecular Medicine Reports - May 12, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate
Publication date: 25 July 2018 Source:Journal of Industrial and Engineering Chemistry, Volume 63 Author(s): Junxiao Ye, Xing Pei, Hui Cui, Zhili Yu, Hyukjin Lee, Jianxin Wang, Xu Wang, Lu Sun, Huining He, Victor C. Yang The covalent attachment of CPPs to siRNA molecules offers great potential for CPP-mediated siRNA delivery. We recently reported a concise and high-yield synthesis strategy of the cell-permeable, cytosol-dissociable LMWP-siRNA covalent conjugate. Herein, cell uptake mechanism and cellular toxicity studies of this conjugate were performed to evaluate the potential of LMWP-siRNA conjugate for clinical transla...
Source: Journal of Industrial and Engineering Chemistry - May 11, 2018 Category: Chemistry Source Type: research
The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells.
Authors: Zhao T, Xu Y, Ren S, Liang C, Zhou X, Wu J Abstract Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL-mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL-mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid...
Source: Experimental and Therapeutic Medicine - May 9, 2018 Category: General Medicine Tags: Exp Ther Med Source Type: research
Effective gene silencing activity of prodrug-type 2'-O-methyldithiomethyl siRNA compared with non-prodrug-type 2'-O-methyl siRNA.
Abstract Small interfering RNAs (siRNAs) are an active agent to induce gene silencing and they have been studied for becoming a biological and therapeutic tool. Various 2'-O-modified RNAs have been extensively studied to improve the nuclease resistance. However, the 2'-O-modified siRNA activities were often decreased by modification, since the bulky 2'-O-modifications inhibit to form a RNA-induced silencing complex (RISC). We developed novel prodrug-type 2'-O-methyldithiomethyl (MDTM) siRNA, which is converted into natural siRNA in an intracellular reducing environment. Prodrug-type 2'-O-MDTM siRNAs modified at th...
Source: Bioorganic and Medicinal Chemistry Letters - May 8, 2018 Category: Chemistry Authors: Hayashi J, Nishigaki M, Ochi Y, Wada SI, Wada F, Nakagawa O, Obika S, Harada-Shiba M, Urata H Tags: Bioorg Med Chem Lett Source Type: research
Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Pre-Specified Secondary End Points in ORION 1.
Conclusions -Inclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting synthesis of PCSK9 through siRNA may be a viable alternative to other approaches which target PCSK9. Clinical Trial Registration -URL: https://www.clinicaltrials.gov. Unique identifier: NCT02597127. PMID: 29735484 [PubMed - as supplied by publisher]
Source: Circulation - May 7, 2018 Category: Cardiology Authors: Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS, Wijngaard P, Kastelein JJ Tags: Circulation Source Type: research
Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
Abstract To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for ...
Source: Biomaterials - May 3, 2018 Category: Materials Science Authors: Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S Tags: Biomaterials Source Type: research
Cell-penetrating peptides for siRNA delivery to glioblastomas
In conclusion, we have established an efficient non-covalently complexed carrier (PF14:TG1) for siRNA delivery to human glioblastoma cells (U87), showing a significant two-fold increase in gene-silencing efficiency compared to the parent peptide PF14 and also improved specificity to U87 cells compared to non-glioma targeted cells. Graphical abstract
Source: Peptides - May 1, 2018 Category: Biochemistry Source Type: research
A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis
A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis, Published online: 01 May 2018; doi:10.1038/s41388-018-0270-8A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis
Source: Oncogene - May 1, 2018 Category: Cancer & Oncology Authors: Simona Pavan Nathalie Meyer-Schaller Maren Diepenbruck Ravi Kiran Reddy Kalathur Meera Saxena Gerhard Christofori Source Type: research
Potential of siRNA-albumin complex against cancer.
Abstract RNA interference is a highly specific as well as efficient technology for gene therapy application in molecular oncology. The present study was planned to develop an efficient and stable tumor selective delivery mechanism for siRNA gene therapy for the purpose of both diagnosis as well as therapy. We have used 20 Male wistar rats for the formation of colon cancer model and utilized albumin as carrier molecule for the delivery of siRNA against vascular endothelial growth factor receptor 2 (VEGF R2). The study results confirmed efficient delivery of siRNA at tumor site as confirmed by tagging of siRNA-album...
Source: Chemico-Biological Interactions - April 27, 2018 Category: Molecular Biology Authors: Liu N, Qi YH, Cheng CT, Yang WB, Malhotra A, Zhou Q Tags: Chem Biol Interact Source Type: research
Co-Delivery of Doxorubicin and Anti-BCL-2 siRNA by pH-Responsive Polymeric Vector to Overcome Drug Resistance in In Vitro and In Vivo HepG2 Hepatoma Model.
In this study, triblock copolymer of poly(ethylene glycol)-block-poly(L-lysine)-block-poly aspartyl (N-(N',N'-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to only bypass drug efflux but also down-regulate the anti-apoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift release at tumors. The codelivered siRNA serves to suppress the expression of anti-apoptotic BCL-2 and conse...
Source: Biomacromolecules - April 24, 2018 Category: Biochemistry Authors: Sun W, Chen X, Xie C, Wang Y, Lin L, Zhu K, Shuai X Tags: Biomacromolecules Source Type: research
AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells.
Authors: Rafael D, Gener P, Andrade F, Seras-Franzoso J, Montero S, Fernández Y, Hidalgo M, Arango D, Sayós J, Florindo HF, Abasolo I, Schwartz S, Videira M Abstract Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Plu...
Source: Drug Delivery - April 20, 2018 Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
Notch-1 siRNA and Methotrexate towards a Multifunctional Approach in Rhematoid Arthritis Management: a Nanomedicine Approach
ConclusionsOverall, nanomedicine-based delivery of MTX and siRNA could overcome the side effects of small molecules and could improve the therapeutic effect of siRNA in rheumatoid arthritis.
Source: Pharmaceutical Research - April 20, 2018 Category: Drugs & Pharmacology Source Type: research
Genome-wide siRNA screening in mouse bone marrow-derived macrophages revealed that knockdown of ribosomal proteins suppresses IL-10 and enhances TNF- α production.
Genome-wide siRNA screening in mouse bone marrow-derived macrophages revealed that knockdown of ribosomal proteins suppresses IL-10 and enhances TNF-α production. J Clin Exp Hematop. 2018 Apr 13;: Authors: Okamura Y, Makita N, Hizukuri Y, Hayashi Y Abstract Macrophages play a central role in the immune response, and their diverse functions are attributed to the spectrum of their functional states. To elucidate molecules involved in modulating the balance between the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine TNF-α, we conducted genome-wide siRNA screening. First, we establishe...
Source: Journal of Clinical and Experimental Hematopathology : JCEH - April 18, 2018 Category: Hematology Tags: J Clin Exp Hematop Source Type: research
Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer
Publication date: Available online 14 April 2018 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Sophia A. Shahin, Ruining Wang, Shirleen I. Simargi, Altagracia Contreras, Liliana Parra, Louise Qu, Wei Wen, Thanh Dellinger, Juli Unternaehrer, Fuyuhiko Tamanoi, Jeffrey I. Zink, Carlotta A. Glackin TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond wel...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - April 15, 2018 Category: Nanotechnology Source Type: research
Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery
Publication date: Available online 21 February 2018 Source:Asian Journal of Pharmaceutical Sciences Author(s): Anna Slita, Anna Egorova, Eudald Casals, Anton Kiselev, Jessica M. Rosenholm Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified t...
Source: Asian Journal of Pharmaceutical Sciences - April 14, 2018 Category: Drugs & Pharmacology Source Type: research
siRNA modified with 2'-deoxy-2'-C-methylpyrimidine nucleosides.
Abstract (2'S)-2'-Deoxy-2'-C-methyluridine and (2'R)-2'-deoxy-2'-C-methyluridine were incorporated in the 3'-overhang region of the sense and antisense strands and in positions 2- and 5- of the seed region of siRNA duplexes directed against Renilla luciferase, while (2'S)-2'-deoxy-2'-C-methylcytidine was incorporated in the 6- position of the seed region of the same constructions. Dual luciferase reporter assay in transfected HeLa cells was used as model system to measure IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine of the antisense 3'-overhang ...
Source: Chembiochem - April 14, 2018 Category: Biochemistry Authors: Dellafiore M, Aviñó A, Alagia A, Montserrat JM, Iribarren AM, Eritja R Tags: Chembiochem Source Type: research
Delivery of siRNA in vitro and in vivo using PEI-capped porous silicon nanoparticles to silence MRP1 and inhibit proliferation in glioblastoma
Multidrug resistance-associated protein 1 (MRP1) overexpression plays a major role in chemoresistance in glioblastoma multiforme (GBM) contributing to its notorious deadly nature. Although MRP1-siRNA transfect...
Source: Journal of Nanobiotechnology - April 13, 2018 Category: Nanotechnology Authors: Wing Yin Tong, Mohammed Alnakhli, Richa Bhardwaj, Sinoula Apostolou, Sougata Sinha, Cara Fraser, Tim Kuchel, Bryone Kuss and Nicolas H. Voelcker Tags: Research Source Type: research
Conserved association of Argonaute 1 and 2 proteins with miRNA and siRNA pathways throughout insect evolution, from cockroaches to flies.
PMID: 29656113 [PubMed - as supplied by publisher]
Source: Biochimica et Biophysica Acta - April 12, 2018 Category: Biochemistry Authors: Rubio M, Maestro JL, Piulachs MD, Belles X Tags: Biochim Biophys Acta Source Type: research
Fine tuning of core-shell structure of hyaluronic acid/cell-penetrating peptides/siRNA nanoparticles for enhanced gene delivery to macrophages in anti-atherosclerotic therapy.
Abstract Hyaluronic acid (HA)-coated LOX-1 specific siRNA-condensed cell-penetrating peptides (CPPs) nanocomplexes were developed for targeted gene delivery to macrophages and suppression of lipid accumulation. The HA coating facilitated the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors and was further degraded by hyaluronidase (HAase) intra plaques for exposing the naked CPPs nanocomplexes (NCs) and achieving the ultimate location into macrophages. The surface coating of HA was verified by the increased particle size, inverted zeta potential, and TEM images. The targeting mechan...
Source: Biomacromolecules - April 11, 2018 Category: Biochemistry Authors: Zhao Y, He Z, Gao H, Tang H, He J, Guo Q, Zhang W, Liu J Tags: Biomacromolecules Source Type: research
GSE97937 microRNA expression profile of MRC5-CAFs transfected with control siRNA (si-Ctrl) or Dicer1 specific siRNA (si-Dicer1) for 72 hr
This study was the first to investigate Dicer1 influence of stromal fibroblast gene expression and the underlying regulation mechanism, which held great importance in complementing our understanding of Dicer1 in OC initiation and development, and raises potent therapeutical targets in controlling OC metastasisWe used microarrays to profile the microRNA expression of MRC5-CAFs before and after Dicer1 knockdown, in order to identify microRNA alteration exerted by Dicer1 in the context of stromal fibroblasts.
Source: GEO: Gene Expression Omnibus - April 10, 2018 Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by array Homo sapiens synthetic construct Source Type: research
GSE97936 Gene expression profile of MRC5-CAFs transfected with control siRNA (si-Ctrl) or Dicer1 specific siRNA (si-Dicer1) for 72 hr
This study was the first to investigate Dicer1 influence of stromal fibroblast gene expression and the underlying regulation mechanism, which held great importance in complementing our understanding of Dicer1 in OC initiation and development, and raises potent therapeutical targets in controlling OC metastasisWe used microarrays to profile the mRNA expression of MRC5-CAFs before and after Dicer1 knockdown, in order to identify molecular alteration exerted by Dicer1 in the context of stromal fibroblasts.
Source: GEO: Gene Expression Omnibus - April 10, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
siRNA - mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.
Abstract The 37kDa/67kDa laminin receptor (LRP/LR) is over-expressed in tumour cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells,...
Source: Experimental Cell Research - April 10, 2018 Category: Cytology Authors: Rebelo TM, Vania L, Ferreira E, Weiss SFT Tags: Exp Cell Res Source Type: research
Water-Soluble Polymer Assists N-Methyl-D-Aspartic Acid Receptor 2B siRNA Delivery to Relieve Chronic Inflammatory Pain In Vitro and In Vivo.
Abstract We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to cells. After transfection, WSLP/NR2B-siRNA complexes reduced the NR2B transcriptional level by 50% and protein level by 55% compared to control siRNA. Moreover, 3 days after intrathecal injection of WSLP/NR2B-siRNA co...
Source: Pain Research and Management - April 8, 2018 Category: Anesthesiology Authors: Peng J, Ma J, Yang X, He H, Wu H, Ma T, Lu J Tags: Pain Res Manag Source Type: research
Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin
Publication date: Available online 7 April 2018 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Canan Schumann, Stephanie Chan, Jess A. Millar, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, gro...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - April 8, 2018 Category: Nanotechnology Source Type: research
Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice.
Authors: Liao W, Qin Y, Liao L, Cen B, Wu Z, Wei Y, Wang Z, Li G, Ji A Abstract Based on successful targeting to the αvβ3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected wi...
Source: Renal Failure - April 7, 2018 Category: Urology & Nephrology Tags: Ren Fail Source Type: research
Rosmarinic acid and siRNA combined therapy represses Hsp27 (HSPB1) expression and induces apoptosis in human glioma cells.
Abstract High expression of Hsp27 in glioma cells has been closely associated with tumor cell proliferation and apoptosis inhibition. The aim of the present study was to asses the effects of rosmarinic acid (RA) on Hsp27 expression and apoptosis in non-transfected and transfected human U-87 MG cells. The effect of rosmarinic acid was compared to quercetin, which is known to be a good Hsp27 inhibitor. In order to block the expression of Hsp27 gene (HSPB1), transfection with specific siRNAs was performed. Western blotting technique was used to assess the Hsp27 expression, and caspase-3 colorimetric activity assay wa...
Source: Cell Stress and Chaperones - April 7, 2018 Category: Cytology Authors: Şengelen A, Önay-Uçar E Tags: Cell Stress Chaperones Source Type: research
Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on siRNA-Mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin
Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - April 7, 2018 Category: Nanotechnology Authors: Canan Schumann, Stephanie Chan, Jess A. Millar, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula Source Type: research
Effect of dihydroarteminin combined with siRNA targeting Notch1 on Notch1/c-Myc signaling in T-cell lymphoma cells.
Authors: Huo L, Wei W, Wu S, Zhao X, Zhao C, Zhao H, Sun L Abstract The effectiveness of therapy combining dihydroartemisinin (DHA) and small interfering RNA targeting Notch1 (siNotch1) in T-cell lymphoma remains unknown. The present study explored the potential and possible mechanisms of combined dihydroarteminin, and siNotch1 therapy for T-cell lymphoma. It was demonstrated that the viability rates of siRNA-DHA-treated cells was significantly suppressed in comparison with those in control cells, control siRNA cells, siRNA-treated cells and DHA-treated cells (P<0.01). Additionally, there was a significant incre...
Source: Experimental and Therapeutic Medicine - March 31, 2018 Category: General Medicine Tags: Exp Ther Med Source Type: research
GSE108262 Comparison of STEEL siRNA-treated and control siRNA-treated human endothelial cells
Contributors : Philip A Marsden ; H S ManSeries Type : Expression profiling by arrayOrganism : Homo sapiensTo determine the role of STEEL in endothelial cell (EC) gene regulation, gene expression analysis was conducted on control and STEEL siRNA-treated human dermal microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs). A total of 225 protein-coding genes were downregulated and 80 were upregulated when both EC types were grouped for analysis. In HMVEC alone, 544 protein-coding genes were downregulated and 218 were upregulated. In HUVEC alone, 177 protein-coding genes were downregulate...
Source: GEO: Gene Expression Omnibus - March 30, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
Complexation of Chol-DsiRNA in place of Chol-siRNA greatly increases the duration of mRNA suppression by polyplexes of PLL(30)-PEG(5K) in primary murine syngeneic breast tumors after i.v. administration
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Vishakha V. Ambardekar, Rajesh R. Wakaskar, Zhen Ye, Stephen M. Curran, Timothy R. McGuire, Don W. Coulter, Rakesh K. Singh, Joseph A. Vetro RNA interference has tremendous potential for cancer therapy but is limited by the insufficient potency of RNAi molecules after i.v. administration. We previously found that complexation with PLL(30)-PEG(5K) greatly increases the potency of 3′-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic 4T1 breast tumors after i.v. administration but mRNA suppress...
Source: International Journal of Pharmaceutics - March 30, 2018 Category: Drugs & Pharmacology Source Type: research
Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease
Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiorgan fibrosis and profoundly affects the quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in the fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amounts of collagen deposits and accumulation of F4/80+ macrophages, as well as myofibroblasts expressing HSP47 and retinol-bin...
Source: Blood - March 29, 2018 Category: Hematology Authors: Yamakawa, T., Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Miyazaki, M., Minomi, K., Onozawa, M., Niitsu, Y., Teshima, T. Tags: Transplantation Source Type: research
Tivanisiran, a novel siRNA for the treatment of dry eye disease.
Authors: Moreno-Montañés J, Bleau AM, Jimenez AI Abstract INTRODUCTION: Dry eye disease (DED) is characterized by an alteration of the tear film with ocular inflammation and neurosensory abnormalities. The main clinical signs of this condition are tear instability and ocular damage. Although DED has gained significant attention in the past few years, limited prescription treatment options are available for patients. Areas covered: The current manuscript summarizes the pre-clinical and clinical development of tivanisiran, a novel small interfering oligonucleotide of RNA (siRNA) used for the treatment of DED. Tivan...
Source: Expert Opinion on Investigational Drugs - March 29, 2018 Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
i-Fect Delivers Again!
Knocks Down Suspected Stress/Anxiety ReceptorThe molecular pathogenesis underlying anxiety disorders is still unclear. Here, the authors demonstrate that myristoylated alanine-rich C-kinase substrate like 1 (MARCKSL1) overexpression in mice increases spine formation in the amygdala and induces stress hormone upregulation and anxiety-like behaviors. Suppression of MARCKSL1 in the amygdala ameliorates both the increase in stress hormones and the elevated anxiety-like behaviors. Our results indicate that MARCKSL1 expression in the amygdala plays an important role in anxiety-like behaviors.This was proved, in part, by the knoc...
Source: siRNA and DsiRNA Transfection Efficiency - March 28, 2018 Category: Neuroscience Tags: Amygdala Anxiety i-Fect MARCKSL1 Stress Source Type: news
Inhibition of BMP4 and Alpha Smooth Muscle Actin Expression in LX-2 Hepatic Stellate Cells by BMP4-siRNA Lipid Based Nanoparticle.
Conclusion: VA-coated liposomes were successfully designed to deliver BMP4-siRNA to specifically target HSC. The novel delivery system discussed herein may serve as a potential therapeutic strategy for the treatment of liver fibrosis in the future. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID: 29578859 [PubMed - in process]
Source: J Pharm Pharm Sci - March 28, 2018 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Alrushaid S, Burczynski FJ, Minuk GY, Gong Y Tags: J Pharm Pharm Sci Source Type: research
Improving Bone Regeneration Using Chordin siRNA Delivered by pH-Responsive and Non-Toxic Polyspermine Imidazole-4,5-Imine
Conclusions: Our results suggest that Chordin is a potential target for improving osteogenesis and bone nonunion therapy and that responsive and non-toxic cationic polyimines such as PSI are therapeutically feasible carriers for the packaging and delivery of Chordin siRNA to hBMSCs.Cell Physiol Biochem 2018;46:133 –147
Source: Cellular Physiology and Biochemistry - March 26, 2018 Category: Cytology Source Type: research
DNA nanoclew templated spherical nucleic acids for siRNA delivery
Chem. Commun., 2018, Advance Article DOI: 10.1039/C7CC09257A, CommunicationWeimin Ruan, Meng Zheng, Yang An, Yuanyuan Liu, David B. Lovejoy, Mingcong Hao, Yan Zou, Albert Lee, Shu Yang, Yiqing Lu, Marco Morsch, Roger Chung, Bingyang Shi A superior biocompatible spherical nucleic acid (SNA) conjugate was fabricated by grafting siRNA onto the surface of a core composed of a spherical DNA nanostructure that we have termed DNA nanoclew (DC). To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - March 23, 2018 Category: Chemistry Authors: Weimin Ruan Source Type: research
GSE112007 Next Generation Sequencing Facilitates Quantitative of Transcriptomes in Various Cells Treated with or without LD100 and siRNA of SOD1
Conclusions: The global transcriptomic data on HeLa, DU145 and RWPE-1 after SOD1 inhibition using its specific inhibitor-LD100 indicated that the most changed expression upon this interruption of ROS homeostasis is the key genes in plenty of signaling pathways inside cancer cells, not inside normal cells, although mRNA levels of numerous genes are altered in three lines of cells. The modulation of gene expression leads to repression of multiple signaling pathways including ERK, PI3K and NF-KB and their crosstalk to promote cell growth and activation of the signaling pathways to cause both cell cycle arrest and apoptosis. T...
Source: GEO: Gene Expression Omnibus - March 23, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research