Search results for "SiRNA"

A New Hyaluronic Acid Derivative Obtained from Atom Transfer Radical Polymerization as a siRNA Vector for CD44 Receptor Tumor Targeting.

2015

Two derivatives of hyaluronic acid (HA) have been synthesized by atom transfer radical polymerization (ATRP), starting from an ethylenediamino HA derivative (HA-EDA) and by using diethylaminoethyl methacrylate (DEAEMA) as a monomer for polymerization. Both samples, indicated as HA-EDA-pDEAEMA a and b, are able to condense siRNA, as determined by gel retardation assay and resulting complexes show a size and a zeta potential value dependent on polymerization number, as determined by dynamic light scattering measurements. In vitro studies performed on HCT 116 cell line, that over express CD44 receptor, demonstrate a receptor mediated uptake of complexes, regardless of their surface charge. New…

Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions

2020

T-cells are a type of lymphocyte (a subtype of white blood cells) that play a central role in cell-mediated immunity. Currently, adoptive T-cell immunotherapy is being developed to destroy cancer cells. In this therapy, T-cells are harvested from a patient&rsquo

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

2015

Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

2016

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in ai…

2015

Abstract High-mobility group box 1 (HMGB1) is a nonhistone protein secreted by airway epithelial cells in hyperinflammatory diseases such as asthma. In order to down-regulate HMGB1 expression in airway epithelial cells, siRNA directed against HMGB1 was delivered through nanocomplexes based on a cationic copolymer of poly(N-2-hydroxyethyl)- d,l -aspartamide (PHEA) by using H441 cells. Two copolymers were used in these experiments bearing respectively spermine side chains (PHEA-Spm) and both spermine and PEG2000 chains (PHEA-PEG-Spm). PHEA-Spm and PHEA-PEG-Spm derivatives complexed dsDNA oligonucleotides with a w/w ratio of 1 and higher as shown by a gel retardation assay. PHEA-Spm and PHEA-P…

Cationic Polyaspartamide as siRNA delivery systems for down regulation of a proinflammatory cytokine

2015

Combining inulin multifunctional polycation and magnetic nanoparticles: Redox-responsive siRNA-loaded systems for magnetofection

2019

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are recognized as one of the most promising agents for theranostic applications. Among methods designed for siRNA delivery, magnetofection, that is, nucleic acid cell uptake under the influence of a magnetic field acting on magnetic nucleic acid vectors, is emerging as a unique approach to combining advantages such as strong improvement of the kinetics of the delivery process and the possibility of localizing nucleic acid delivery to an area where the magnetic field is applied. This paper reports on the preparation of siRNA loaded magnetoplexes&mdash

Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells

2017

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gen…

Dual-targeting siRNAs.

2010

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been develo…

Identification of pathways involved in aneuploidy onset and its tolerance using a DNA microarray approach

2013

Genomic instability is a hallmark of the majority of human tumors explaining the heterogeneity shown by tumor cells. This phenomenon is often associated with chromosomal instability (CIN) and aneuploidy, a condition in which tumor cells lose or gain chromosomes. Previously, we showed that posttranscriptional silencing by RNAi of pRb1, DNMT12 and MAD2 is associated with aneuploidy in cultured human cells reinforcing the idea that there are several roads leading to aneuploidy. In the attempt to understand if a common molecular signature exists underlying aneuploidy and its tolerance in tumor cells, we induced aneuploidy in human fibroblasts (IMR90) by depleting Rb, MAD2 and DNMT1 genes and an…