Genotoxicity of poly(propylene imine) dendrimers

Abstract

Dendrimers are highly branched macromolecules with the potential in biomedical applications. Due to positively charged surfaces, several dendrimers reveal toxicity. Coating peripheral cationic groups with carbohydrate residues can reduce it. In this study, the cytotoxicity and genotoxicity of three types of 4th generation poly(propylene imine) dendrimers were investigated. Peripheral blood mononuclear cells (PBMCs) were treated with uncoated (PPI-g4) dendrimers, and dendrimers in which approximately 40% or 90% of peripheral amino groups were coated with maltotriose (PPI-g4-OS or PPI-g4-DS) at concentration of 0.05, 0.5, 5 mg/ml. Abbreviations OS and DS stand for open shell and dense shell respectively, that describes the structure of carbohydrate modified dendrimers. After 1 h of cell incubation at 37°C, the MTT and comet assays were performed. PPI dendrimers demonstrated surface-modification-degree dependent toxicity, although genotoxicity of PPI-g4 and PPI-g4-OS measured by the comet assay was concentration dependent up to 0.5 mg/ml and at 5 mg/ml the amount of DNA that left comet's head decreased. Results may suggest a strong interaction between dendrimers and DNA, and furthermore, that coating PPI dendrimers by maltoriose is an efficient method to reduce their genotoxicity what opens the possibilities to use them as therapeutic agents or drug carriers.

Influence of fourth generation poly(propyleneimine) dendrimers on blood cells

“…PPI‐g4 and PPI‐g4‐OS can interact with negatively charged cell membranes owing to their positively charged surfaces and this interaction may block the access of the mitogen to receptors on the cell surface. It is also possible that the lack of proliferation is a consequence of dendrimer genotoxicity 53–56. Because they are able to interact with nucleic acids,7 dendrimers bind to DNA or RNA after entering the nucleus.…”

Impact of structural differences in hyperbranched polyglycerol–polyethylene glycol nanoparticles on dermal drug delivery and biocompatibility

“…For example, cationic phosphoruscontaining dendrimers induced DNA damage in human mononuclear blood cells, A549 human cancer cells, and human gingival fibroblasts [56]. Similar findings were published for poly(propylene imine) dendrimers and again a clear correlation between surface charge and interactions with the DNA was drawn [57]. Dendrimers mainly interact with nucleic acids on the basis of ionic interactions between the negatively charged backbone phosphate groups and positively charged amino groups of the polymer.…”

Blockage of Wnt/β‐Catenin Signaling by Nanoparticles Reduces Survival and Proliferation of CLL Cells In Vitro—Preliminary Study

“…We assume that the higher activity of the PPI‐G4‐OS‐M3 dendrimer result from its structure—the presence of free surface amino groups and positive charge allow for stronger bonding to negatively charged cellular structures. [16a,18] It can be seen in the speed of action (the cytotoxic effect visible after 4 h incubation; Table ) and the number of genes that have been influenced by the dendrimer in question. Results of the independent Ann/PI assay with M3 used at concentrations of 4 and 10 mg mL −1 indicated that the sugar itself does not show any toxicity to MEC‐1 cells (Table S1 and Figure S1, Supporting Information), thus we assume, that it has no influence on gene expression.…”