Search results for "gene delivery."
showing 10 items of 95 documents
Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery
2020
Polysarcosine (pSar) is a polypeptoid based on the endogenous amino acid sarcosine (N-methylated glycine), which has previously shown potent stealth properties. Here, lipid nanoparticles (LNPs) for therapeutic application of messenger RNA were assembled using pSarcosinylated lipids as a tool for particle engineering. Using pSar lipids with different polymeric chain lengths and molar fractions enabled the control of the physicochemical characteristics of the LNPs, such as particle size, morphology, and internal structure. In combination with a suited ionizable lipid, LNPs were assembled, which displayed high RNA transfection potency with an improved safety profile after intravenous injection…
Synthesis and bio-functionalization of magnetic nanoparticles for medical diagnosis and treatment
2011
The synthesis of multifunctional magnetic nanoparticles (NPs) is a highly active area of current research located at the interface between materials science, biotechnology and medicine. By virtue of their unique physical properties magnetic nanoparticles are emerging as a new class of diagnostic probes for multimodal tracking and as contrast agents for MRI. Furthermore, they show great potential as carriers for targeted drug and gene delivery, since reactive agents, such as drug molecules or large biomolecules (including genes and antibodies), can easily be attached to their surface. On the other hand, the fate of the nanoparticles inside the body is mainly determined by the interactions wi…
Hydrophilic and hydrophobic copolymers of a polyasparthylhydrazide bearing positive charges as vector for gene therapy
2008
BACKGROUND: The design of polymeric vectors for gene delivery provided with specific properties is one of the most critical aspects for a successful gene therapy. These polymers should be biocompatible as well as able to carry efficiently DNA to target tissues and to transfect it into cells. RESULTS: The formation of complexes of poly[(α,β-asparthylhydrazide)–poly(ethylene glycol)] and poly[(α,β-asparthylhydrazide)–hexadecylamine] copolymers functionalised with glycidyltrimethylammonium chloride (PAHy–PEG-GTA and PAHy–C16-GTA, respectively) with DNA was studied. The effects of the introduction of hydrophilic (PEG) or hydrophobic (C16) moieties on the chains of PAHy–GTA copolymers, such as t…
Gene delivery agents possessing antiradical activity: self-assembling cationic amphiphilic 1,4-dihydropyridine derivatives
2013
Seventeen 1,4-dihydropyridine (1,4-DHP) amphiphiles including differently substituted pyridinium, pyrazinium, N-methyl piperidinium or N-methyl morpholinium moieties as the cationic head-group of the molecule have been designed and synthesised. 1,4-DHP amphiphiles have been earlier proposed as a promising tool for plasmid DNA (pDNA) delivery in vitro. In this work the ability of the 1,4-DHP amphiphiles to self-assemble, to bind pDNA and to transfer it into the cells as well as the cytotoxicity of 1,4-DHP amphiphiles–pDNA complexes was studied. Furthermore, antiradical activity (ARA) of the 1,4-DHP derivatives was determined. We have revealed that all new 1,4-DHP amphiphiles possessed self-a…
Oligonucleotides-decorated-poly(N-vinyl pyrrolidone) nanogels for gene delivery
2013
Pulsed electron-beam irradiation of a semi-dilute poly(N-vinyl pyrrolidone) (PVP) aqueous solution in the presence of acrylic acid has led to a carboxyl functionalized nanogel system. Nanoparticles hydrodynamic size and surface charge density, in water and as a function of pH, were investigated by dynamic light scattering and laser doppler velocimetry, respectively. Nanogels (NGs) were proved not to be cytotoxic at the cellular level. Indeed, they rapidly bypass the cellular membrane to accumulate in specific cell portions of the cytoplasm, in the perinuclear area. The availability of pendant carboxyl groups on the crosslinked PVP NGs core prompted us to attempt their decoration with a sing…
Systematic Study of a Library of PDMAEMA-Based, Superparamagnetic Nano-Stars for the Transfection of CHO-K1 Cells.
2017
The introduction of the DNA into mammalian cells remains a challenge in gene delivery, particularly in vivo. Viral vectors are unmatched in their efficiency for gene delivery, but may trigger immune responses and cause severe side-reactions. Non-viral vectors are much less efficient. Recently, our group has suggested that a star-shaped structure improves and even transforms the gene delivery capability of synthetic polycations. In this contribution, this effect was systematically studied using a library of highly homogeneous, paramagnetic nano-star polycations with varied arm lengths and grafting densities. Gene delivery was conducted in CHO-K1 cells, using a plasmid encoding a green fluore…
Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation.
2011
Even though it is known for more than one decade that antigen-encoding RNA can deliver antigenic information to induce antigen-specific immunity against cancer, the nature and mechanism of RNA uptake have remained enigmatic. In this study, we investigated the pharmacokinetics of naked RNA administered into the lymph node. We observed that RNA is rapidly and selectively uptaken by lymph node dendritic cells (DCs). Furthermore, in vitro and in vivo studies revealed that the efficient internalization of RNA by human and murine DCs is primarily driven by macropinocytosis. Selective inhibition of macropinocytosis by compounds or as a consequence of DC maturation abrogated RNA internalization and…
PREPARAZIONE E CARATTERIZZAZIONE DI NANOSISTEMI LIPIDICI PER IL DIREZIONAMENTO E IL RILASCIO MODIFICATO DI FARMACI E ACIDI NUCLEICI IN TERAPIA ONCOLO…
2016
sono stati sviluppati sistemi nanoparticellari in grado di intrappolare elevate quantità di farmaci e di legare materiale genico. I sistemi preparati sono stati caratterizzati da un punto di vista chimico-fisico e tecnologico farmaceutico. Sono stati infine utilizzati per prove in vitro e i risultati ottenuti hanno mostrato che essi possiedono le caratteristiche per potere essere considerati dei validi carrier per farmaci e materiale genico nel trattamento oncologico.
Mechanisms of cell death in canine parvovirus-infected cells provide intuitive insights to developing nanotools for medicine
2010
Jonna Nykky, Jenni E Tuusa, Sanna Kirjavainen, Matti Vuento, Leona GilbertNanoscience Center and Department of Biological and Environmental Science, University of Jyväskylä, FinlandAbstract: Viruses have great potential as nanotools in medicine for gene transfer, targeted gene delivery, and oncolytic cancer virotherapy. Here we have studied cell death mechanisms of canine parvovirus (CPV) to increase the knowledge on the CPV life cycle in order to facilitate the development of better parvovirus vectors. Morphological studies of CPV-infected Norden laboratory feline kidney (NLFK) cells and canine fibroma cells (A72) displayed characteristic apoptotic events. Apoptosis was f…
Well-defined polypeptide-based systems as non-viral vectors for cytosolic delivery
2017
A convenient cytosolic drug delivery constitutes a very powerful tool for the treatment and/or prevention of several relevant human diseases. Along with recent advances in therapeutic technologies based on biomacromolecules (e.g. oligonucleotides or proteins), we also require the development of technologies which improve the transport of therapeutic molecules to the cell of choice. This has led to the emergence of a variety of promising methods over the last 20 years. Despite significant progress, these methods still suffer from several shortcomings including low/variable delivery efficiency, high cytotoxicity, and perhaps most importantly, ineffective endosomal/lysosomal escape. In this co…