Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers have been widely used in medical applications. However, PAMAM dendrimers bearing amino terminals show certain cytotoxicity. In order to improve their biocompatibility, we modified Generation-5 PAMAM dendrimers by conjugating them with poly(ethylene glycol) (PEG) of two different molecular weights and different number of chains. The IC(50) values of PEGylated dendrimers were 12-105 fold higher than those of PAMAM dendrimers. To investigate the influence of PEGylation on PAMAM-induced cytotoxicity, the intracellular responses, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and apoptosis were examined. The results indicated that conjugation with PEG could effectively reduce the PAMAM-induced cell apoptosis by attenuating the ROS production and inhibiting PAMAM-induced MMP collapse. Meanwhile, dendrimers conjugated with less PEG of lower molecular weight did not significantly change the endocytic properties. Dendrimers conjugated with more PEG of higher molecular weight were much less cytotoxic. This study provided a novel insight into the effects of PEGylation on the decrease of cytotoxicity at the molecular level.
Microbial biofilms can cause severe problems in technical installations where they may give rise to microbially influenced corrosion and clogging of filters and membranes or even threaten human health, e.g. when they infest water treatment processes. There is, hence, high interest in methods to prevent microbial adhesion as the initial step of biofilm formation. In environmental technology it might be desired to enhance bacterial transport through porous matrices. This motivated us to test the hypothesis that the attractive interaction energy allowing cells to adhere can be counteracted and overcome by the shear force induced by electroosmotic flow (EOF, i.e. the water flow over surfaces exposed to a weak direct current (DC) electric field). Applying EOF of varying strengths we quantified the deposition of Pseudomonas fluorescens Lp6a in columns containing glass collectors and on a quartz crystal microbalance. We found that the presence of DC reduced the efficiency of initial adhesion and bacterial surface coverage by >85%. A model is presented which quantitatively explains the reduction of bacterial adhesion based on the extended Derjaguin, Landau, Verwey, and Overbeek (XDLVO) theory of colloid stability and the EOF-induced shear forces acting on a bacterium. We propose that DC fields may be used to electrokinetically regulate the interaction of bacteria with surfaces in order to delay initial adhesion and biofilm formation in technical installations or to enhance bacterial transport in environmental matrices.
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