Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles

Abstract The influence of size, surface charge and surface functionality of poly(amido amine) dendrimers and silica nanoparticles (SNPs) on their toxicity was studied in immunocompetent mice. After systematic characterization of nanoparticles, they were administered to CD-1 (caesarean derived-1) mice to evaluate acute toxicity. A distinct trend in nanotoxicity based on surface charge and functional group was observed with dendrimers regardless of their size. Amine-terminated dendrimers were fatal at doses >10 mg/kg causing haematological complications such as disseminated intravascular coagulation-like manifestations whereas carboxyl- and hydroxyl-terminated dendrimers of similar sizes were tolerated at 50-fold higher doses. In contrast, larger SNPs were less tolerated than smaller SNPs irrespective of their surface functionality. These findings have important implications in the use of these nanoparticles for various biomedical applications.

[1]  M. Bryszewska,et al.  Interactions between PAMAM dendrimers and bovine serum albumin. , 2003, Biochimica et biophysica acta.

[2]  R L Vessella,et al.  Biotin reagents for antibody pretargeting. 3. Synthesis, radioiodination, and evaluation of biotinylated starburst dendrimers. , 1998, Bioconjugate chemistry.

[3]  P. Swaan,et al.  Surface acetylation of polyamidoamine (PAMAM) dendrimers decreases cytotoxicity while maintaining membrane permeability. , 2007, Bioconjugate chemistry.

[4]  Xiao-Dong Zhou,et al.  In vitro toxicity of silica nanoparticles in human lung cancer cells. , 2006, Toxicology and applied pharmacology.

[5]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[6]  E. W. Meijer,et al.  Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Donald A Tomalia,et al.  Dendrimers in biomedical applications--reflections on the field. , 2005, Advanced drug delivery reviews.

[8]  W. Chan,et al.  Nanotoxicity: the growing need for in vivo study. , 2007, Current opinion in biotechnology.

[9]  Ron C. Hardman A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[10]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[11]  J. Hermans,et al.  Fibrin: Structure and Interactions , 1982, Seminars in thrombosis and hemostasis.

[12]  Chin-Tu Chen,et al.  Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles. , 2010, Biomaterials.

[13]  H. Roberts,et al.  Effect of lysosomal cationic proteins from polymorphonuclear leukocytes upon the fibrinogen and fibrinolysis system. , 1975, Thrombosis research.

[14]  E. Gabellieri,et al.  Dendrimer-protein interactions studied by tryptophan room temperature phosphorescence. , 2006, Biochimica et biophysica acta.

[15]  M. Caputi,et al.  Structure, function and antagonists of urokinase-type plasminogen activator. , 2009, Frontiers in bioscience.

[16]  D. Tomalia Starburst/Cascade Dendrimers: Fundamental building blocks for a new nanoscopic chemistry set , 1994 .

[17]  Alisa S Wolberg,et al.  Thrombin generation and fibrin clot structure. , 2007, Blood reviews.

[18]  W. Bode,et al.  Structure and interaction modes of thrombin. , 2006, Blood cells, molecules & diseases.

[19]  M Laird Forrest,et al.  Effects of nanomaterial physicochemical properties on in vivo toxicity. , 2009, Advanced drug delivery reviews.

[20]  D. Tomalia,et al.  Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. , 2001, Drug discovery today.

[21]  H. Weetall,et al.  Preparation of immobilized proteins covalently coupled through silane coupling agents to inorganic supports , 1993, Applied biochemistry and biotechnology.

[22]  A. Vrij,et al.  Synthesis and characterization of colloidal dispersions of fluorescent, monodisperse silica spheres , 1992 .

[23]  Robert Langer,et al.  The biocompatibility of mesoporous silicates. , 2008, Biomaterials.

[24]  B. Furie,et al.  Thrombus formation in vivo. , 2005, The Journal of clinical investigation.

[25]  Claudia Fruijtier-Pölloth Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. , 2005, Toxicology.