Herein, we mainly summarize several types of chemical transfection methods based on nanocarriers, which include calcium phosphates, lipids, and cationic polymers like chitosan, PEI, polyamidoamine dendrimers, poly (lactide-co-glycolide) and so on. On one hand, we discuss the mechanisms underlying these approaches as well as their achievements and, on the other hand, we compare their relative advantages and potential therapeutic applications in research, preclinical and clinical medicine.
Several types of PAMAM dendrimers have been tested as gene vectors for gene therapy15. Experiments showed that PAMAM dendrimers are effective transfection agents, providing high successful rate of transferring genetic materials into the cell. Dendrimers also tested in boron neutron capture therapy15. It is possible to attach boron complexes and antibodies on the surface of the dendrimer. While the antibodies target at the cancer cells, the boron complexes capture neutrons from an external source and release energetic radiation that can kill the cancer cells.
Gene transfer methods are promising in the field of gene therapy. Current methods for gene transfer include three major groups: viral, physical and chemical methods. This review mainly summarizes development of several types of chemical methods for gene transfer and by means of nano-carriers like; calcium phosphates, lipids, and cationic polymers including chitosan, polyethylenimine, polyamidoamine dendrimers, and poly(lactide-co-glycolide). This review also briefly introduces applications of these chemical methods for gene delivery.
Originally, this biological effect was said to be the result of inhibition of lipopolysaccharide synthesis. (21) More recent evidence points to a different molecular target, the NAD(P)H-dependent enoyl acyl carrier protein reductase. (22) This enzyme is involved in the last reductive step of fatty acid synthase in bacteria, and the structure of the inhibitory complex with diazaborines in the presence of the nucleotide cofactor. This was clearly demonstrated by X-ray crystallography. (23) Interestingly, in the X-ray structure is found a covalent bond between boron, in a tetracoordinated geometry, and the 2’hydroxyl of the nicotinamide ribose. (6)
Convergent growth (ref 22)the attachment of the outermost functional groups to an inner generation and the attachment of the inner generations to the core. The structural units before the final attachment to the core is called the "wedge." Usually, three to four wedges attach to the core. Each wedge can have different functional groups at the periphery. Thus, the making of unsymmetrical dendrimers is possible. This modification is useful in monolayer formation at the organic-aqueous interface11. Half of the dendrimer is submerged in the water phase, while the other half is in the organic phase. A combination of these two methods can be use to suit for special needs. 3.Potential Applications of Dendrimers3.1. Medicinal ApplicationsThe idea of dendrimer serving as host for foreign molecules was first stumble upon by Meijer12. He trapped several small molecules (Bengal Rose dye) in the cavities of water soluble dendrimer molecules with a diameter about 5 nm. The "dendritic box" is a fifth generation poly (propylene imine) consisting of 64 functional groups at the periphery. The trapped foreign molecules cannot diffuse out of the box. Only upon prolong heating, the trapped molecules were able to escape. It is possible to use the "dendritic box" as vehicle for drug delivery. Meijer’s group has been designing a box that could be opened enzymatically or photochemically. This unique feature is also explored by Tomalia’s group13. The capability of hosting small organic molecules in water is the key to transport biological molecules. Frechet’s group at Cornell is working on a dendrimer for chemotherapy14. A chemotherapeutic drug is weakly bonded to the periphery of a dendrimer. Other functional groups add to the dendrimer to increase water solubility. Once the dendrimer reaches its target, the bond between the drug and the dendrimer is cleaved (enzymatically or photochemically). Since dendrimers are inert and stable, they are nontoxic to human. It was shown that dendrimers could eliminate through the kidneys as urine14. Willich, a German scientist is working on a dendrimer for magnetic resonance angiography and is currently entering clinical trials15. The dendrimer is polylysine with gadolinium ion complexes on the end groups. Dendrimer provides multiple bonding sites on the periphery, allowing many MRI contrasting agent complexes to attach to one dendrimer. One dendrimer molecule can host up to twenty-four contrasting agent complexes and hence attaining higher signal-to-noise ratio15. The dendrimer prevents any complex from diffusing into untargeted area. Thus, a better contrast MRI picture is obtained. Several types of PAMAM dendrimers have been tested as gene vectors for gene therapy15. Experiments showed that PAMAM dendrimers are effective transfection agents, providing high successful rate of transferring genetic materials into the cell. Dendrimers also tested in boron neutron capture therapy15. It is possible to attach boron complexes and antibodies on the surface of the dendrimer. While the antibodies target at the cancer cells, the boron complexes capture neutrons from an external source and release energetic radiation that can kill the cancer cells. 3.2. Dendrimer Films Frechet’s group at Cornell is working on polyether dendrimers films that can isolate metal ions3. His target application is for signal amplification in fiber-optic communication technology. Apparently, his dendrimer coatings on the metal ions are able to prevent interference between ions when they excited by light. Crooks and Well at A&M are exploring the possibilities of using dendrimer films as sensitive interfaces for sensing applications16. The dendrimers formed a thin monolayer film onto a gold surface. When it exposed to volatile organic compounds, the film was able to capture the volatile molecules. The contains of the film were then analyzed by a device called surface acoustic wave mass balance. The functionalities on the periphery of the dendrimer molecule could be modified to sense different organic compounds selectivly16. Dendrimer films also serve as anti-corrosive coating on metal surfaces. The film is able to trap corrosive agent in the dendritic cavities, preventing any diffusion to the surface of the metal16. 3.3. Interphases Applications As previously discussed, the convergent method is able to make unsymmetrical dendrimers. This arrangement allows the dendrimers to form monolayers at the gas-liquid interfaces or aqueous-organic interfaces17. Amphiphilic dendrimer are useful in forming interfacial liquid membranes for stabilizing aqueous-organic emulsion (Figure 8). One other application is to use dendrimer film to extract chemical compounds between two phases. Dendrimers with carboxylate chain ends can form micelles in water. Their hydrophobic interiors dissolve organic molecules that are insoluble in water. They act like carrier for organic molecules in aqueous phase. This arrangement holds promise for the development of organic chemistry in aqueous medium17. Hydrophilic dendrimers with hydrophobic functionalities on the periphery form micelles in organic solvents. These types of dendrimers can extract organic compound from the water phase to the organic phase5. Dendrimers films also can use as purifiers. They can selectively permit molecules to diffuse through the interface17. 3.5. Catalysis and Reaction SitesCatalysis is one of the most promising applications in dendrimer research. Dendrimers have nanoscopic cavities that act like microenvironment for molecular reactions5. The cavities provide nanoscale reactor sites for catalysis. There are two possible catalytic sites being investigated, one at the core and the other at the surface respectively. Many attempts have been made on using dendrimers to enhance reaction rate and reaction selectivity. There is a micropolarity around the core, thereby influencing its molecular recognition and catalytic properties14. One of the possible schemes for catalytic reaction in water is shown in figure 8. It is found that dendrimers are very useful in enantiomeric catalysis. Bolm et al had developed a dendrimer catalysis for enantioselective for reduction of benzaldehyde18. The dendritic cavities provide a confined environment
B., Synthesis of azide-alkyne fragments for click' chemical applications; formation of oligomers from orthogonally protected trialkylsilyl-propargyl azides and propargyl alcohols.
His research interests are focused in the chemistry of polyphenolic and nitrogen heterocyclic compounds, with special emphasis on the development of new synthetic routes and also on organocatalytic and metal-catalyzed transformations. His group has been centered in the development of sustainable synthetic methods, by using microwave irradiation and solvent free conditions; more recently the group developed the first static ohmic heating reactor for chemical synthesis at laboratory scale, a high energy-efficient way of heating chemical reactions using water as solvent. Using this alternative heating method, new protocols for the synthesis of relevant compounds have already been successfully developed. His research interests also include the isolation and structural characterization of natural products from diverse terrestrial and marine sources.
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