Shielding siRNA by peptide-based nanofibers: An efficient approach for turning off EGFR gene in breast cancer.

Peptide-based self-assembled nanosystems show great promise as non-viral gene and siRNA delivery vectors. In the current study, we designed and functionalized nanofibers for the delivery of siRNA, targeting and silencing EGFR gene overexpressed in triple-negative breast cancer. The nanofiber-mediated siRNA delivery was characterized in terms of zeta potential, morphology, and structural stability by circular dichroism spectroscopy.

Synthesis and biophysical evaluation of carbosilane dendrimers as therapeutic siRNA carriers.

Gene therapy presents an innovative approach to the treatment of previously incurable diseases. The advancement of research in the field of nanotechnology has the potential to overcome the current limitations and challenges of conventional therapy methods, and therefore to unlocking the full potential of dendrimers for use in the gene therapy of neurodegenerative disorders. The blood-brain barrier (BBB) poses a significant challenge when delivering therapeutic agents to the central nervous system.

Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity.

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g.

Silver Nanoparticles Modified by Carbosilane Dendrons and PEG as Delivery Vectors of Small Interfering RNA.

The fact that cancer is one of the leading causes of death requires researchers to create new systems of effective treatment for malignant tumors. One promising area is genetic therapy that uses small interfering RNA (siRNA). These molecules are capable of blocking mutant proteins in cells, but require specific systems that will deliver RNA to target cells and successfully release them into the cytoplasm.

The effect of surface modification of dendronized gold nanoparticles on activation and release of pyroptosis-inducing pro-inflammatory cytokines in presence of bacterial lipopolysaccharide in monocytes.

Biomedical applications of gold nanoparticles (AuNPs) may be limited by their toxicological effects. Although surface-modified AuNPs can induce apoptosis, less is known about whether they can induce other types of cell death. Pyroptosis, an inflammatory type of programmed cell death, can be induced in immune cells, especially macrophages, by bacterial endotoxins.

Prospects of Cationic Carbosilane Dendronized Gold Nanoparticles as Non-viral Vectors for Delivery of Anticancer siRNAs siBCL-xL and siMCL-1.

Cancer is one of the most important problems of modern medicine. At the present time, gene therapy has been developed against cancer, which includes the delivery of anticancer small interfering RNAs (siRNAs) directed at cancer proteins. The prospect of creating drugs based on RNA interference implies the use of delivery systems.

Comparison of the effects of dendrimer, micelle and silver nanoparticles on phospholipase A2 structure.

The interaction of nanoparticles (NP) with proteins (the so-called 'protein corona') is a huge challenge in attempting to apply them in personalized nanomedicine. We have analyzed the interaction between A) two 'soft' NPs (a cationic phosphorus dendrimer of generation 3; a cationic phosphorus amphiphilic dendron of generation 2), and B) one 'hard' nanoparticle (silver NP covered with cationic carbosilane dendritic moieties); and membrane-bound protein phospholipase A2 from bovine pancreas. The hard and soft NPs have differences in the nature of their interactions with phospholipase A2.

PEGylation of Dendronized Gold Nanoparticles Affects Their Interaction with Thrombin and siRNA.

The use of nonviral carriers based on nanomaterials is a promising strategy for modern gene therapy aimed at protecting the genetic material against degradation and enabling its efficient cellular uptake. To improve the effectiveness of nanocarriers , they are often modified with poly(ethylene glycol) (PEG) to reduce their toxicity, limit nonspecific binding by proteins in the bloodstream, and extend blood half-life. Thus, the selection of an appropriate degree of surface PEGylation is crucial to preserve the interaction of nanoparticles with the genetic material and to ensure its efficient transport to the site of action.

Dendronized Gold Nanoparticles as Carriers for gp160 (HIV-1) Peptides: Biophysical Insight into Complex Formation.

The unavailability of effective and safe human immunodeficiency virus (HIV) vaccines incites several approaches for development of the efficient antigen/adjuvant vaccination composite. In this study, three different dendronized gold nanoparticles (AuNPs 13-15) were investigated for a complexation ability with gp160 synthetic peptides derived from an HIV envelope. It has been shown that HIV peptides interacted with nanoparticles as evident from the changes in their secondary structures, restricted the mobility of the attached fluorescence dye, and enhanced peptide helicity confirmed by the fluorescence polarization and circular dichroism results.

Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA.

Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl).

Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery.

The disruption of the cellular pathways of protein biosynthesis through the mechanism of RNA interference has been recognized as a tool of great diagnostic and therapeutic significance. However, in order to fully exploit the potential of this phenomenon, efficient and safe carriers capable of overcoming extra- and intracellular barriers and delivering siRNA to the target cells are needed. Recently, attention has focused on the possibility of the application of multifunctional nanoparticles, dendrimers, as potential delivery devices for siRNA.

Nanoparticles in Combating Cancer: Opportunities and Limitations. A Brief Review.

Nanomedicine is a good alternative to traditional methods of cancer treatment but does not solve all the limitations of oncology. Nanoparticles used in anticancer therapy can work as carriers of drugs, nucleic acids, imaging agents or they can sensitize cells to radiation. The present review focuses on the application of nanoparticles to treating cancer, as well as on its problems and limitations.

Effect of PEGylation on the biological properties of cationic carbosilane dendronized gold nanoparticles.

Heterofunctionalized gold nanoparticles (AuNPs) were obtained in a one pot reaction of gold precursor with cationic carbosilane dendrons (first to third generations, 1-3G) and (polyethylene)glycol (PEG) ligands in the presence of a reducing agent. The final dendron/PEG proportion on AuNPs depends on the initial dendron/PEG ratio (3/1, 1/1, 1/3) and dendron generation. AuNPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet spectroscopy (UV-VIS), thermogravimetric analysis (TGA), nuclear magnetic resonance (H NMR) and zeta potential (ZP).

Role of cationic carbosilane dendrons and metallic core of functionalized gold nanoparticles in their interaction with human serum albumin.

Functionalization of gold nanoparticles by different chemical groups is an important issue regarding the biomedical applications of such particles. Therefore we have analyzed the interaction between gold nanoparticles functionalized by carbosilane dendrons with human serum albumin at different pHs, and in the presence of the protein unfolding agent, guanidine hydrochloride, using circular dichroism, zeta-potential and fluorescence quenching. The effect of a nanoparticle dendronization and pure dendrons on the immunoreactivity of albumin was estimated using ELISA.

Dendronization of gold nanoparticles decreases their effect on human alpha-1-microglobulin.

Gold nanoparticles are new kinds of nanomaterials. Their large surface-to-volume ratio, stability, excellent biocompatibility, low toxicity and functionality make them very attractive for biomedical applications. Therefore we have analyzed how dendronized gold nanoparticles interact with human alpha-1-microglobulin.

Original Multivalent Gold(III) and Dual Gold(III)-Copper(II) Conjugated Phosphorus Dendrimers as Potent Antitumoral and Antimicrobial Agents.

Original metallophosphorus dendrimers (generation 3, 48 terminal groups) have been prepared via the complexation of phosphorus dendrimers bearing imino-pyridino end groups with Au(III) or with both Au(III) and Cu(II). The complexation of the dendrimer with Au(III), leading to 1G3-[Au][AuCl], strongly increased the antiproliferative activities against both KB and HL-60 tumoral cell lines, showing ICs in the low nanomolar range. It can be noticed also that this gold conjugated phosphorus dendrimer displayed low activity on the quiescent cell line EPC versus its potent antiproliferative activity against actively dividing cells.

Antibacterial and antifungal properties of dendronized silver and gold nanoparticles with cationic carbosilane dendrons.

Water soluble silver nanoparticles (AgNPs) capped with cationic carbosilane dendrons have been synthesized by direct reaction in water of dendrons, silver precursor and a reducing agent. These nanoparticles have been characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), ultraviolet spectroscopy (UV), elemental analysis, and zeta potential (ZP). The antibacterial and antifungal properties of the cationic dendrons and dendronized AgNPs and AuNPs with these dendrons have been evaluated against Gram-negative and Gram-positive bacterial -including resistant strains- and yeast strains, respectively.

Binding of poly(amidoamine), carbosilane, phosphorus and hybrid dendrimers to thrombin-Constants and mechanisms.

Thrombin is an essential part of the blood coagulation system; it is a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, and catalyzes many other coagulation-related reactions. Absorption at its surface of small nanoparticles can completely change the biological properties of thrombin. We have analyzed the influence on thrombin of 3 different kinds of small nanoparticles: dendrimers (phosphorus-based, carbosilane based and polyamidoamine) and 2 hybrid systems containing carbosilane, viologen and phosphorus dendritic scaffolds in one single molecule, bearing different flexibility, size and surface charge.

Dendrimer-protein interactions versus dendrimer-based nanomedicine.

Dendrimers are hyperbranched polymers belonging to the huge class of nanomedical devices. Their wide application in biology and medicine requires understanding of the fundamental mechanisms of their interactions with biological systems. Summarizing, electrostatic force plays the predominant role in dendrimer-protein interactions, especially with charged dendrimers.

Gold nanoparticles stabilized by cationic carbosilane dendrons: synthesis and biological properties.

Gold nanoparticles (AuNPs) and polycationic macromolecules are used as gene carriers. Their behaviour is dependent on several factors, such as the size and type of the framework, charge, etc. We have combined both types of systems and prepared AuNPs covered with cationic carbosilane dendrons with the aim to evaluate their biocompatibility.

Oleochemical-tethered SBA-15-type silicates with tunable nanoscopic order, carboxylic surface, and hydrophobic framework: cellular toxicity, hemolysis, and antibacterial activity.

Novel silicates were prepared by using silylated natural fatty acids (derived from triglyceride renewable oils) as co-condensing reagents in presence of tetraethyl orthosilicate (TEOS) and the triblock copolymer, pluronic P123, as a structure directing agent. A series of carboxylic acid functionalized SBA-15-type mesoporous silicates were obtained with tunable nanoscopic order and reactive functional groups that allow the conjugation of amino probes by peptide coupling. Photophysical studies of the covalently linked aminopyrene substantiated that the internal framework of these materials have pronounced hydrophobicity.

Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts.

We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some oxygen-silicon bonds that are unstable in water.

Novel 'Si-C' carbosilane dendrimers as carriers for anti-HIV nucleic acids: studies on complexation and interaction with blood cells.

Treatment of HIV infection by gene therapy is a promising tool for combating AIDS. One of the primary limitations of gene therapy is the effective delivery of nucleic acids to the target cells. Dendrimers are nanoparticles that are increasingly being used as nucleic acid vehicles.

Phosphorus dendrimers as carriers of siRNA--characterisation of dendriplexes.

There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation.

Highly organized self-assembled dendriplexes based on poly(propylene imine) glycodendrimer and anti-HIV oligodeoxynucleotides.

Dendrimers are artificial polymeric macromolecules which are widely considered to be a promising tool for future gene therapy applications. They have been used as efficient delivery vehicles for antisense oligonucleotides targeting the interior of cells. We demonstrate that dendriplexes formed from anti-HIV oligodeoxynucleotides ANTI-TAR, GEM91, and SREV in complex with generation 4 maltose (PPI-Mal G4) and maltotriose (PPI-Mal-III G4) modified poly(propylene imine) dendrimers are able to self-assemble into highly organized 1D and 3D nanostructures.