Modification Of Dendrimers Research Articles

Polyamidoamine dendrimer-modified polyvinylidene fluoride microporous membranes for protein separation

The separation efficiency of pressure-driven filtration membranes is primarily dictated by the membrane pore size. Membranes with larger pores typically demonstrate high flux but low or zero rejection when it comes to separating small molecules. In protein separation, ultrafiltration (UF) membranes with pore sizes smaller than the molecular dimensions of target proteins are commonly used for size rejection. Taking inspiration from the separation mechanism of nanofiltration (NF) membranes, we hypothesize that introducing charged groups into membranes of appropriate pore sizes could significantly enhance the electrical interaction between membrane charges and protein charges. This enhancement, occurring at the nanoscale distance when protein molecules approach or pass through charged nanoscale membrane channels, may enable the rejection of proteins substantially smaller than the pore size. Using membranes with relatively large pore sizes could lead to an increase in flux. To test this hypothesis, we conducted experiments involving the modification of polyvinylidene fluoride (PVDF) membranes with suitable pore sizes, using polyamidoamine (PAMAM) dendrimers to introduce negative charges to the membranes. The performance of the PVDF membranes and the modified membranes were investigated in the separation of whey proteins. To evaluate the contribution of steric and electrical hindrance to the solute separation, filtration experiments were performed using polyethylene oxide (PEO) and polyacrylic acid (PAA). The membranes were characterized using techniques such as attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). The results indicate that the modification enhances the rejection efficiency of whey proteins. The whey protein rejection and permeate flux for PVDF membranes were 58.9% and 15.3 LMH, respectively. Following alkaline treatment or PAMAM-G3.5 dendrimer modification, the whey protein rejection increased to 97.3% and 98.8%, respectively. However, alkaline treatment and PAMAM-G3.5 dendrimer modification resulted in a reduction of permeate flux to 5.6 LMH and 2.3 LMH, respectively. This suggests that increasing membrane charge effectively enhances the separation ability of filtration membranes in charged macromolecule separation.

Polyphenolic dendrimers as carriers of anticancer siRNA

Dendrimers have emerged as an important group of nanoparticles to transport drugs, DNA, or RNA into target cells in cancer and other diseases. Various functional modifications can be imposed on dendrimers to increase the efficacy and specificity in delivering their cargo to the target cells and decrease their toxicity. In the present work, we evaluated the potential of carbosilane polyphenolic dendrimers modified with caffeic acid (CA) and polyethylene glycol (PEG) to deliver proapoptotic Mcl-1 and Bcl-2 siRNAs to A549 cancer cells. Dendrimers formed stable complexes with siRNAs as assessed by transmission electron microscopy and gel electrophoresis. Modification of dendrimers with PEG reduced the size and the zeta potential of dendrimer/siRNA complexes. The presence of PEG caused a red shift of the CD spectrum, and this effect was the more pronounced, the higher the dendrimer/siRNA ratio was. The nanocomplexes were internalized by A549. All studied dendrimer/siRNA formulations inhibited tumor cell migration and adhesion and caused an increase in the population of early apoptotic cells. Among four tested dendrimers, the polyphenolic compound containing two caffeic acid moieties complexed with siRNA demonstrated the lowest polydispersity index and showed an excellent transfection profile. In conclusion, this dendrimer are a promising candidate for the delivery of siRNA into cancer cells in further in vivo studies.

Dendrimer Modification Strategy Based on the Understanding of the Photovoltaic Mechanism of a Perovskite Device under Full Sun and Indoor Light

The wide-band-gap inorganic CsPbI2Br perovskite material provides a highly matched absorption range with the indoor light spectrum and is expected to be used in the fabrication of highly efficient indoor photovoltaic cells (IPVs) and self-powered low-power Internet of Things (IoT) sensors. However, the defects that cause nonradiative recombination and ion migration are assumed to form leakage loss channels, resulting in a severe impact on the open-circuit voltage (VOC) and the fill factor (FF) of IPVs. Herein, we introduce poly(amidoamine) (PAMAM) dendrimers with multiple passivation sites to fully repair the leakage channels in the devices, taking into account the characteristics of IPVs that are extremely sensitive to nonradiative recombination and shunt resistance. The as-optimized IPVs demonstrate a promising PCE of 35.71% under a fluorescent light source (1000 lux), with VOC increased from 0.99 to 1.06 V and FF improved from 75.21 to 84.39%. The present work provides insight into the photovoltaic mechanism of perovskites under full sun and indoor light, which provides guidance for perovskite photovoltaic technology with industrialization prospects.

Pyridine terminated polyurethane dendrimer/chlorinated butyl rubber nanocomposites with excellent mechanical and damping properties

Due to the special viscoelastic property, traditional rubber with high performance has been widely used in human life and production. However, it is challenging to improve the damping property without sacrificing the extensibility. In this work, a novel type of second-generation polyurethane dendrimer terminated with pyridine (G2-Py) was synthesized by using thiolactone chemistry and subsequently complexed with Zn ions. The structure and morphology of G2-Py were characterized. G2-Py-Zn2+ was then mixed with chlorinated butyl rubber (CIIR) by a two-roll mill. A series of CIIR/G2-Py-Zn2+ elastomers were obtained through vulcanization. CIIR/G2-Py-Zn2+ elastomers could achieve high stretchability (a strain of ∼1035%), high mechanical strength (a tensile stress of 7.64 MPa). This was benefitted from the friction between G2-Py and CIIR as well as variety of non-covalent bonds provided by G2-Py-Zn2+, which can dissipate energy to further improve the strength and extensibility. The coordination of Zn2+-pyridine was confirmed by Fourier transform infrared spectroscopy, stress relaxation and cycle tensile test. To further investigate the morphology and damping properties of the elastomers, scanning electron microscopy and dynamic mechanical analysis were performed. CIIR-5 showed the best damping performance with higher tanδmax and wider effective damping temperatures. Therefore, this dendrimer modification technology provides wider applications for CIIR elastomers in daily life.

Preparation of PAMAM dendrimer modified amidoxime chelating resin and its adsorption for U(VI) in aqueous

• Amidoxime resin modified by PAMAM was synthesized for uranium adsorption. • Dendrimer modification greatly improved the adsorption capacity of the chelating resin. • PAMAM modification had little effect on the adsorption selectivity of U(VI). • The introduction of PAMAM reduced the desorption rate of the chelating resin. Uranium adsorption materials need to consider both adsorption capacity and selectivity. Based on the high adsorption capacity of polyamidoamine (PAMAM) dendrimer and the high selectivity of amidoximated (AO) resin for U(VI), a novel PAMAM modifed AO chelating resin (PS-PAMAM-AO) was prepared and used for U(VI) adsorption in aqueous. For comparison, a common AO resin (PS-AO) was prepared based on ammoniated poly(styrene- co -divinylbenzene) bead (PS-NH 2 ). The synthesized resins were characterized by Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The factors affecting adsorption such as solution pH and temperature, contact time and initial U(VI) concentration were investigated. PS-PAMAM-AO had the largest adsorption capacity (167.8 mg/g, at pH 5.0 and 313 K with initial U(VI) concentration 300 mg/L) compared with its precursor (PS-NH 2 and PS-PAMAM) and PS-AO. Kinetic and thermodynamic studies showed its U(VI) adsorption was a chemical and rate-limiting process and conformed to the Langmuir isothermal model. The adsorbed U(VI) can be desorbed with 10 % NaCl + 1 mol/L HCl, and the desorption rate reached 94.1 %. When the concentration of coexisting NaCl increased from 0.0 to 1.0 mol/l, the U(VI) adsorption capacity of PS-PAMAM-AO decreased to 69.9 %, similar to that of PS-AO (77.4 %), PAMAM modification did not significantly affect the adsorption selectivity of amidoximated resin.

Diphenolic acid-modified PAMAM/chlorinated butyl rubber nanocomposites with superior mechanical, damping, and self-healing properties

ABSTRACT Based on its excellent damping properties, traditional rubber has been widely used in various industries, including aerospace, rail transit and automotive. However, the disadvantages of effective damping area, unstable damping performance, easy fatigue, and aging, greatly limited the further application of rubber materials. Thus, it is important to develop novel modified rubber damping materials. Herein, polyamidoamine dendrimers with terminal-modified phenolic hydroxyl and amine groups (G2 PAMAM-H) were designed and used as modifiers to improve the damping performance of chlorinated butyl rubber (CIIR). The results showed that the modification of G2 PAMAM by diphenolic acid can avoid its aggregation in the CIIR matrix. CIIR/G2 PAMAM-H nanocomposites exhibited high tan δ max of 1.52 and wide damping temperature region of 140°C (tan δ > 0.55)at a very low loading (4.32 wt.%), which were strongerthan that of pure CIIR and CIIR/G2 PAMAM nanocomposites. In addition, these nanocomposites also exhibited a unique self-healing ability by multiple hydrogen bonds, which can effectively extend the life of the rubber material in actual production. Therefore, the dendrimer modification provided unique development opportunities for elastomers in certain highly engineered fields, such as vehicles, rail transit, aerospace, etc.

AN UPDATED REVIEW ON THE APPLICATION OF DENDRIMERS AS SUCCESSFUL NANOCARRIERS FOR BRAIN DELIVERY OF THERAPEUTIC MOIETIES

It’s been nearly 100 y of effort to study the organization and role of the blood brain-barrier and still, we strive to find better techniques to overcome this barrier to deliver the drugs to the brain effectively with reduced systemic side effects. The advances in nanotechnology have given newer horizons in achieving this goal since the nano-scaled systems can modify an existing drug to have a high degree of sensitivity to the physiological conditions and specificity to reach the target organ. Among the various nanocarriers, dendrimers owing to their unique physical and chemical characteristics, represent a potential therapeutic tool in biomedical and pharmaceutical science. Dendrimers, an established polymeric nanocarrier system of the time, can deliver both drugs and genetic material and are being extensively studied to target the brain. The surface modification of dendrimers can reduce their innate toxicity problems and increase the therapeutic efficacy of brain disorders. This review article is an attempt to update on the potential of dendrimers explored in the past five years as a drug delivery avenue that can be considered as a promising solution in the management of a wide range of disorders affecting the central nervous system, including neoplastic, degenerative, and ischemic conditions. The following search criteria were used to expand the review article with the keywords dendrimers, novel drug delivery, nanoparticles, site-specific drug delivery etc.

Starburst Poly(amidoamine) Dendrimer Grafted Gold Nanoparticles as a Scaffold for Folic Acid-Targeted Plasmid DNA Delivery In Vitro.

Gene therapy has opened doors for the treatment of genetic disorders such as cancer. However, it clinical application has been limited by safety-efficacy issues. Recently, dendritic stabilized metal nanoparticles have shown great potential as efficient non-viral modalities for plasmid DNA delivery. This study involved the synthesis, characterisation, evaluation of the cytotoxicity profiles, and ability of unmodified and folic acid modified poly(amidoamine) generation 5 dendrimer grafted gold nanoparticles to deliver plasmid DNA containing a luciferase gene to cancer cells in vitro. Unmodified and folic acid modified poly(amidoamine) generation 5 dendrimer nanoparticles were also evaluated for comparative studies. Nanocomplexes prepared with folic acid unmodified/modified poly(amidoamine) grafted gold nanoparticles and plasmid DNA were characterized by transmission electron microscopy, nanoparticle tracking analysis, ultra-violet spectroscopy, nuclear magnetic resonance, band shift, dye displacement and nuclease protection assays. Cytotoxicity profiles and gene expression were evaluated in five mammalian cell lines, using the MTT cell viability and luciferase reporter gene assays respectively. Nanocomplexes at optimum w/w ratios of 5.2:1 and 6.0:1, protected the plasmid DNA against serum nucleases and were well tolerated by all cell lines. Transgene expression was higher with folic acid modified dendrimer grafted gold nanoparticles, in folic acid-receptor overexpressing tested cells, compared to that of the control dendrimer nanoparticles, decreasing significantly (p <0.05) in the presence of excess folic acid ligand, confirming nanocomplex uptake to be via receptor mediation. Overall, the transfection efficiency of the dendrimer modified gold nanocomplexes superseded that of the control dendrimer nanocomplexes indicating the importance of dendrimer modification and the significant role of gold nanoparticles in the formulation of these delivery systems.

Multiscale Molecular Simulations Applied to Nucleic Acid-Dendrimer Interactions Studies

As shown in the present review, molecular dynamics simulations can contribute by studying at theoretical level dendrimer-nucleic acid complexes at different conditions, such as pH or ionic strength. Therefore, different cell conditions such as the stay at the cytoplasm and the transit towards endosomes can be addressed. The influence of different terminal groups of dendrimers to DNA/RNA binding can also be evaluated using molecular simulations and especially, by using free energy methods, which aim to determine affinity of dendrimers for nucleic acids. The development of a library of terminal groups for dendrimers may represent a significant contribution to the design of new dendrimers. In this regard, protein-DNA interactions of structure databases have been analyzed as a way to identify suitable residues that can be incorporated as terminal groups of dendrimers. In summary, computational chemistry and biology tools will aim the design of new dendrimers for different kinds of cargo molecules.

Active Release of Nitric Oxide-Releasing Dendrimers from Electrospun Polyurethane Fibers.

The fabrication of electrospun composite polyurethane fibers capable of dual-action antibacterial dendrimer release is reported. Generation 4 (G4) poly(amidoamine) dendrimers were functionalized with octyl alkyl chain or quaternary ammonium (QA) moieties followed by modification of the resulting secondary amines with N-diazeniumdiolate nitric oxide (NO) donors to produce dual-action antibacterial dendrimers. Control and NO-releasing dendrimers were doped into polyurethane solutions prior to electrospinning of the polymer to yield well-defined dendrimer-doped composite polyurethane fibers. The fiber mats were semi-porous (≥30% porosity) and exhibited high water uptake (>100% relative to fiber mass). Dendrimer- and NO-release characteristics (rates and totals) were dependent on the dendrimer modification and polyurethane composition, with total dendrimer- and NO-release amounts ranging from 10 - 80 μg/mg and 0.027 - 0.072 μmol NO/mg, respectively. The antibacterial action of the fibers was evaluated against Gram-negative and Gram-positive bacterial strains. Nitric oxide-releasing fibers demonstrated broad-spectrum bactericidal action at short (2 h) and long (24 h) timescales.

Biocompatible Size-Defined Dendrimer-Albumin Binding Protein Hybrid Materials as a Versatile Platform for Biomedical Applications.

For the design of a biohybrid structure as a ligand-tailored drug delivery system (DDS), it is highly sophisticated to fabricate a DDS based on smoothly controllable conjugation steps. This article reports on the synthesis and the characterization of biohybrid conjugates based on noncovalent conjugation between a multivalent biotinylated and PEGylated poly(amido amine) (PAMAM) dendrimer and a tetrameric streptavidin-small protein binding scaffold. This protein binding scaffold (SA-ABDwt) possesses nM affinity toward human serum albumin (HSA). Thus, well-defined biohybrid structures, finalized by binding of one or two HSA molecules, are available at each conjugation step in a controlled molar ratio. Overall, these biohybrid assemblies can be used for (i) a controlled modification of dendrimers with the HSA molecules to increase their blood-circulation half-life and passive accumulation in tumor; (ii) rendering dendrimers a specific affinity to various ligands based on mutated ABD domain, thus replacing tedious dendrimer-antibody covalent coupling and purification procedures.

Anomalous Reflection of Gold: A Novel Platform for Biochips.

The importance of protein detection system for protein functions analyses in recent post-genomic era is rising with the emergence of label-free protein detection methods. We are focusing on a simple and practical label-free optical-detection method called anomalous reflection (AR) of gold. When a molecular layer forms on the gold surface, significant reduction in reflectivity can be observed at wavelengths of 400-500 nm. This allows the detection of molecular interactions by monitoring changes in reflectivity. In this chapter, we describe the AR method with three different application platforms: (1) gold, (2) gold containing alloy/composite (AuAg2O), and (3) metal-insulator-metal (MIM) thin layers. The AuAg2O composite and MIM are implemented as important concepts for signal enhancement process for the AR technique. Moreover, the observed molecular adsorption and activity is aided by a three-dimensional surface geometry, performed using poly(amidoamine) or PAMAM dendrimer modification. The described system is suitable to be used as a platform for high-throughput detection system in a chip format.

Maltose modified poly(propylene imine) dendrimers as potential carriers of nucleoside analog 5′-triphosphates.

Poly(propylene imine) (PPI) dendrimers contained surface maltose modification are proposed as drug carriers for nucleoside analog (NA) 5′-triphosphates. The aim of this study was to investigate the interactions between PPI dendrimers of 3rd (G3) or 4th (G4) generation and cytidine-5′-triphosphate (CTP) by Isothermal Titration Calorimetry method. CTP was used as a model molecule of pyrimidine nucleoside analog—cytarabine (ara-CTP) commonly used in leukemia treatment. Complexes of PPI dendrimers with NAs may help to overcome severe limitations of NAs associated with their low solubility and stability or resistance in cancer cells. In the present work, we evaluated stoichiometry and a mechanism of forming complexes between dendrimers and the nucleotide. Moreover, we examined the efficiency of complex formation in relation to dendrimer generations, a type of dendrimer modification with maltose residues and a type of solvent. It was observed that PPI dendrimers create complexes with CTP with high efficiency that makes them promising candidates for a drug delivery system.

Development of TRPN dendrimer-modified disordered mesoporous silica for CO2 capture

A novel series of tri(3-aminopropyl) amine (TRPN) dendrimers were synthesized and impregnated on structurally disordered mesoporous silica (DMS) to generate CO2 adsorbents (TS). The physicochemical and adsorption properties of the adsorbents before and after dendrimer modification were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and N2 adsorption–desorption (N2-BET) techniques. CO2 adsorption–desorption tests indicated that the sorbent demonstrates high CO2 adsorption capacity (138.1mgg−1 for G1 sample TS-G1-3CN-50 and 91.7mgg−1 for G2 sample TS-G2-6CN-50), and can completely desorb CO2 under vacuum at 60°C. Its CO2 adsorption capacity at 25°C increases with the amine loading, achieving the highest adsorption capacity (140.6mgg−1 for TS-G1-3CN) at 60%. The developed TS materials exhibited excellent cycling stability. After 12 consecutive adsorption–desorption runs, TS-G1-3CN-50 shows an adsorption capacity of 136.0mgg−1, retaining 98.5% of its original value.

Regulation of Photophysical Properties for Naphthyl Decorated PAMAM Dendrimers by Pseudorotaxane Formation at Periphery

Abstract Dendrimers are regularly and hierarchically branched synthetic macromolecules with monodispersity, globular shape, interior pockets, and numerous peripherial functionality, which endow them with great potential in miscellaneous applications such as host-guest chemistry, chemosensor, catalysis, drug delivery, microreactor and light-harvesting systems. In the present work, a series of naphthyl terminal-decorated polyamidoamine (PAMAM) dendrimers Gn-NA (n=1~3) and model compound were synthesized. The water-soluble PAMAM backbone was constructed by the classic divergent method and the terminal modification of dendrimers by naphthyl groups was accomplished through a reaction of peripheral amino units with naphthyl succinimidyl ester efficiently. The average functionalization extents of the peripheral groups were 100%, 97% and 93% for G1~G3, respectively. The structures of Gn-NA (n=1~3) were characterized by H NMR, C NMR, MALDI-TOF mass spectra and IR. Steady state and time-resolved photophysical studies reveal that strong interactions among peripheral naphthyls occur within Gn-NA, resulting in the excimer formation and the naphthyl fluorescence quenching. The quenching efficiency of naphthyl fluorescence increases with increasing generations. The assembly of the peripheral naphthyl group with cucurbit[7]uril (CB[7]) forms a pseudorotaxane with ratio of 1∶1 and association constants (an application of B-H equation) of 768, 887 and 823 mol•L from generation 1 to generation 3, respectively. The lifetime of the pseudorotaxane of NA-Model with CB[7] is slightly longer than that of NA-Model, indicating that the formation of pseudorotaxane can reduce the nonradiative decay at a certain degree. The lifetimes of naphthyl group and its pseudorotaxane with CB[7] of Gn-NA were resolved to be 2.5~2.7 and 11.4~11.7 ns, respectively, and the lifetimes of the intramolecular naphthyl excimer of Gn-NA were analyzed to be ca. 17 ns. Combining the results of the remarkably increased lifetime of the naphthyl group in its pseudorotaxane form and those of the NA-Model system, we conclude that the peripheral pseudorotaxane formation depresses both the formation of intramolecular naphthyl excimer and the excited state quenching by solvent, thus enhancing the fluorescence emission of naphthyl dramatically. This study provides a potential strategy for developing controllable light-emitting dendritic system with efficient synthesis and improvable photophysical properties.

The Model Construction and Structures of the Dendronized SWCNTs Collaborative Nano-Materials

The dendronized SWCNTs collaborative nanomaterials were designed by grafting the dendrimers to the surfaces of the SWCNTs (11, 5) based on the interface characteristics of the dendrimer. The results based on molecular dynamics studies shown that the dendrimer modifications formed spiral parallel coated structures after grafting, which probably amplified the chirality of the SWCNTs (11, 5) and used in chirality recognition. 0G dendrimer modification makes the surface of the SWNCTs produce more point outshoots, and the modification is with a better parallel position to the carbon nanotube. These point outshoots increased the active points on the surfaces of the SWCNTs, which maybe lead to high field emission performance.

Development of surface chemistry for surface plasmon resonance based sensors for the detection of proteins and DNA molecules

The immobilisation of biological recognition elements onto a sensor chip surface is a crucial step for the construction of biosensors. While some of the optical biosensors utilise silicon dioxide as the sensor surface, most of the biosensor surfaces are coated with metals for transduction of the signal. Biological recognition elements such as proteins can be adsorbed spontaneously on metal or silicon dioxide substrates but this may denature the molecule and can result in either activity reduction or loss. Self assembled monolayers (SAMs) provide an effective method to protect the biological recognition elements from the sensor surface, thereby providing ligand immobilisation that enables the repeated binding and regeneration cycles to be performed without losing the immobilised ligand, as well as additionally helping to minimise non-specific adsorption. Therefore, in this study different surface chemistries were constructed on SPR sensor chips to investigate protein and DNA immobilisation on Au surfaces. A cysteamine surface and 1%, 10% and 100% mercaptoundecanoic acid (MUDA) coatings with or without dendrimer modification were utilised to construct the various sensor surfaces used in this investigation. A higher response was obtained for NeutrAvidin immobilisation on dendrimer modified surfaces compared to MUDA and cysteamine layers, however, protein or DNA capture responses on the immobilised NeutrAvidin did not show a similar higher response when dendrimer modified surfaces were used.

Coarse-grained molecular simulation of interacting dendrimers

We consider the effective interaction between dendrimers affected by pH and counterions of solution as well as terminal modification of dendrimers through the calculation of the free energy with coarse-grained molecular dynamics simulations. We find that the decrease of the pH value can induce the increase in the effective size of dendrimers and that multivalent counterions can lead to like-charged attraction between dendrimers. Under high-valent counterion conditions, the attractive force between the two dendrimers displays the “M”-like profiles induced by the competition of various interactions. Moreover, short modification of surface does not change their trend of aggregation no matter what the terminal monomers of the dendrimers are. Our results are helpful for designing a novel class of dendrimers to achieve optimal functionalities.

Influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers.

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6-8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers. In vitro cell biological assays show that amine, hydroxyl, and acetamide-terminated G5 dendrimers with positive, slightly positive, and close to neutral surface charges, respectively are able to deliver 2-ME to inhibit cancer cell growth. In contrast, 2-ME complexed with carboxyl-terminated G5 dendrimers with negative surface charges does not show its inherent bioactivity. Further molecular dynamics simulation studies show that the compact structure of carboxylated G5 dendrimers complexed with 2-ME does not allow the release of the drug molecules even at a pH of 5.0, which is the typical pH value in lysosome. Our findings indicate that the surface modification of dendrimers with different charges is crucial for the development of formulations of various anticancer drugs for therapeutic applications.

202. Effect of Modification with Lipophilic Fragments and Inclusion of Endosomolytic Peptide on Transfection Efficiency Mediated by Lysine Dendrimers

Development of effective non-viral DNA carriers is considered to be a perspective approach for DNA delivery into eucaryotic cells with gene therapy aims. Our research was devoted to group of asymmetric lysine dendrimers. We studied fifth generation dendrimer D5 and its analog D5C10 which was modified by capric acid residues in external sphere. All vehicles were investigated for their capacity to bind DNA (using gel-retardation and ethidium bromide exclusion assay) and to provide protection plasmid DNA from nuclease degradation (using DNAse I protection test). Transfectional capacity of dendrimers were tested according to the efficiency of beta- galactosidase gene expression in HeLa cells. Modification of dendrimers by capric residues resulted in increase of ability to bind and to protect DNA from enzymatic degradation. Besides, D5C10 provides 10-fold more effective DNA delivery into cells, compared to D5. Addition of endosomolytic peptide JTS-1 to DNA/dendrimer complexes resulted in significant increase of gene delivery with dendrimers, especially with D5C10. The transfection effectiveness for DNA/D5C10/JTS-1 reached 16%. Thus we demonstrate that D5 and D5C10 carriers are perspective vehicles for DNA delivery into cells and can be basis for the development of more effective modular non-viral systems.