Immobilization of Ligand‐Modified Polyamidoamine Dendrimer for Cultivation of Hepatoma Cells

Abstract

Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. The core part of these polymers, tris(2-aminoethyl)amine, was immobilized onto polystyrene plates to which animal cells do not adhere. using photoreactive 4-(3-trifluoromethylazirino) benzoyl-N-succinimide (TDBA-OSu). Cells of a rat hepatoma cell line, H4-II-E-C3, adhered to a surface immobilized with a first-generation dendrimer probably through interactions between the terminal amino groups of the dendrimer and the cell membranes. The adhered cells were viable, could proliferate, and exhibited urea synthetic activity. The modification of the terminal amino groups with fructose increased the final number of cells obtained after 5 days of cultivation. Multigeneration dendrimers were prepared by repeated linkage of tris(2-aminoethyl)amine with the amino groups. Theoretically, the number of terminal amino groups available for ligand modification is twice as much for each generation of dendrimer growth. Cells cultivated on multigeneration fructose-modified dendrimers exhibited enhanced urea synthetic activity. The use of ligand-modified dendrimers is, therefore, considered to be very promising for the construction of bioartificial organs based on cultivation of the animal cells.

Polyethylene glycol‐based cationically charged hydrogel beads as a new microcarrier for cell culture

“…The cell densities between 1 × 10 5 and 2.5 × 10 5 cells/cm 2 were reported for the cultivation of rat hepatoma cells on polyamidoamine dendrimer immobilized polystyrene culture plates 45. The cell density was found to be 3 × 10 4 cells/cm 2 in the cultivation of human endothelial cells on peptide‐carrying polymethacrylate‐coated glass substrate 46.…”

Enhanced biological stability of collagen with incorporation of PAMAM dendrimer

“…The increased cell viability at the low concentration of dendrimer may be due to the increased cell interaction between the terminal cationic amine groups of the dendrimer and the cells. This interaction may lead to the increased cell adherence and proliferation as the immobilization of the dendrimer was previously reported to modify polystyrene plates for promoting cell adherence due to the electrostatic attraction 31. In addition, the conjugation of growth factors/peptides onto terminal group of dendrimer has been used to provide higher selectivity and biological recognition 32, 33.…”

“…This interaction may lead to the increased cell adherence and proliferation as the immobilization of the dendrimer was previously reported to modify polystyrene plates for promoting cell adherence due to the electrostatic attraction. 31 In addition, the conjugation of growth factors/peptides onto terminal group of dendrimer has been used to provide higher selectivity and biological recognition. 32,33 Thus in our case, PAMAM dendrimer may also attract negatively charged proteins or growth factors in the serum to promote biological recognitions and lead to the increased cell growth.…”

Mixed‐ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids

“…This is considered advantageous for cell attachment or stimulation of cells via ligands. Fructose 11 and the tripeptide growth factor 12 glycyl-Lhistidyl-L-lysine enhanced the liver-specific function of hepatoma cells when they were used as ligands. Moreover, we showed that fructose-modified dendrimers suppress apoptosis of primary-cultured hepatocytes and maintain the number of initially adhered hepatocytes without a decline in cell function.…”