title: First evidences of PAMAM dendrimer internalization in microorganisms of environmental relevance: A linkage with toxicity and oxidative stress.
abstract: This article reports novel results on the toxic mechanisms of action of amine- and hydroxyl-terminated poly(amidoamine) (PAMAM) dendrimers toward microorganisms of environmental relevance, namely a cyanobacterium of the genus Anabaena and the green alga Chlamydomonas reinhardtii. We used PAMAM ethylenediamine core dendrimers from generations G2 to G4, which displayed a positive charge, measured as ζ-potential, in culture media. All amine-terminated and most remarkably the G4 hydroxyl-terminated dendrimer inhibited the growth of both microorganisms. The effect on the growth of the green alga was significantly higher than that on the cyanobacterium. With concentrations expressed in terms of molarity, there was a clear relationship between dendrimer generation and toxicity, with higher toxicity for higher generation. Hormesis was observed for hydroxyl-terminated dendrimers at low concentrations. The cationic dendrimers and G4-OH significantly increased the formation of reactive oxygen species (ROS) in both organisms. ROS formation was not related with the chloroplast or photosynthetic membranes and photosystem II photochemistry was unaffected. Cell damage resulted in cytoplasm disorganization and cell deformities and was associated to an increase in ROS formation and lipid peroxidation in mitochondria in the green alga; cell wall and membrane disruption with apparent loss of cytoplasmic contents was found in the cyanobacterium. It was determined for the first time that cationic PAMAM dendrimers were quickly and largely internalized by both organisms. These results warn against the generalization of the use of dendrimers, which may pose significant risk for the environment and particularly for primary producers which are determinant for the health of natural ecosystems.
authors.affiliation: Departamento de Ingeniería Química, Universidad de Alcalá , Alcalá de Henares, Madrid , Spain .
authors.forename: Soledad
authors.initials: S
authors.lastname: Gonzalo
authors.forename: Ismael
authors.initials: I
authors.lastname: Rodea-Palomares
authors.forename: Francisco
authors.initials: F
authors.lastname: Leganés
authors.forename: Eloy
authors.initials: E
authors.lastname: García-Calvo
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosal
authors.forename: Francisca
authors.initials: F
authors.lastname: Fernández-Piñas
mesh_terms: D017033:Anabaena / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016825:Chlamydomonas reinhardtii / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D017753:Ecosystem; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010788:Photosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical
keywords: Algae; PAMAM dendrimers; cyanobacteria; internalization; mitochondrial damage