Design and Synthesis of Triazole-Based Peptide Dendrimers.

Chemical vectors for gene delivery based on only one kind of pure materials, such as lipid or chitosan, have not only their special advantages but also their intrinsic deficiencies which are difficult to resolve. To improve the transfection efficiency and reduce the cytotoxicity, many researchers have focused on combining two or more kinds of materials to enhance the transfection efficiency and at the same time avoiding the side effects to the cells []. Dendron-bearing lipids with PAMAM G1 designated as DL-G1-2C18 have been synthesized. In spite of less efficient cellular uptake of the lipoplexes, they generated free pDNA molecules in the cytosol more effectively than other lipoplexes did [].

Metal mediated synthesis of heterocycles and dendrimers.

T1 - DNA-directed synthesis of generation 7 and 5 PAMAM dendrimer nanoclusters

Synthesis of PAMAM Dendrimer Derivatives with …

Lauterbur, Wiener and Tomalia pioneered the use of dendrimer-based MRI contrast agents by reporting some of the highest known relaxivities for these agents 77, 78. These extraordinary properties have been studied extensively in vivo during the last decade by Kobayashi and Brechbiel. These properties appear to result from a combination of the geometrical amplification of chelated gadolinium that is possible on a dendrimers surface and higher rotational correlation times with minimal segmental motion that are intrinsic to these dendrimer conjugates. Consequently, dendrimer-based Gd(III) chelates consisting of generations 2 and 6 PAMAM dendrimers with 12 and 192 terminal surface amines conjugated to the chelating ligand 2-(4-isothiocyanatobenzyl)-6-methyl diethylene triamine pentaacetic acid through a thiourea linkage were synthesized and used in vivo with rabbits. These contrast agents exhibited excellent MRI images of blood vessels upon intravenous injection. The blood circulation times were sufficiently long, with more than 100 min for large dendrimer conjugates such as the G = 6 PAMAM-TU-Gd(III) - DTPA 79, 80.

Convergent Synthesis of Internally Branched PAMAM Dendrimers

Boron Neutron Capture Therapy: Boron neutron capture therapy is a cancer treatment based on a nuclear capture reaction. When 10B is irradiated with low energy or thermal neutrons, highly energetic a-particles and 7Li ions are produced that are toxic to tumor cells. To achieve the desired effects, it is necessary to deliver 10B to tumor cells at a concentration of at least 109 atoms per cell. One study, involving intratumoral injection of a conjugate between PAMAM dendrimer G5 carrying 1100 boron atoms at its surface and cetuximab, the monoclonal antibody specific for the EGF receptor, showed that the conjugate was present at an almost 10-fold higher concentration in brain tumors than in normal brain tissue 81.

Functionalization of high generation PAMAM dendrimers to achieve higher transfection efficiency.

Synthesis of PAMAM Dendrimer-Based Fast Cross …

Hong et al., explicitly quantified the binding avidity of multi-valent targeted G5-PAMAM containing different numbers of folic acid molecules Binding avidity to folic acid receptor-over expressing cells increased with each additionally bound FA molecule conjugated to the dendrimer, saturating at 5-6 moieties per dendrimer, though the rate of intracellular internalization was not significantly affected with increased binding. The dendrimers demonstrated a dramatic enhancement of binding avidity of almost 5 orders of magnitude. It was suggested that aggregates of 5-6 FA receptors are pre organized on the membrane and that the key factor in reported tumor reduction is enhanced residence time on the cell and not the rate of endocytosis 57.

PAMAM dendrimers with porphyrin core: synthesis …

Wang et al., synthesized polyhydroxyalkanoate (PHA) matrix restraining PAMAM dendrimers penetrated quantity of tamsulosin through snake skin was 15.7 µg/cm2 /d and 24µg/cm2 /d from PHA and PAMAM dendrimers containing PHA matrices, correspondingly. It is found that PAMAM dendrimers enhances the diffusion of tamsulosin. They concluded that the PAMAM dendrimers itself does not voyage in the interior of the skin; however, it takes steps as polymeric skin permeation enhancer by altering the macroscopic constitution of water in the solution 48, 54.

Synthesis and cytotoxic activity of G3 PAMAM-NH2 …

Dendrimers in Gene Transfection: Dendrimers can act as vectors, in gene therapy. Amino-terminated PAMAM or PPI dendrimers as non-viral gene transfer agents, enhancing the transfection of DNA by endocytosis and, ultimately, into the cell nucleus 71, 72. Dendrimers of high structural flexibility and partially degraded high- generation dendrimers (i.e., hyper branched architectures) appear to be better suited for certain gene delivery operations due to their enhanced flexibility, which allows the formation of more compact complexes with DNA. It has been found that maximum transfection efficiency is obtained with a net positive charge on the complexes (i.e., an excess of primary amines over DNA phosphates) 73, 74, 75. Kukowska-Latallo et al. reported that intravenous administration of G9 PAMAM dendrimer-complexed pCF1CAT plasmid could result in high level of gene expression in the lung tissues of rats. It enhances the transfection efficiency and expression pattern of dendrimers 76.