title: Surface charge determines the lung inflammogenicity: A study with polystyrene nanoparticles.
abstract: Surface functionalization is a routine process to improve the behavior of nanoparticles (NPs), but the induced surface properties, such as surface charge, can produce differential toxicity profiles. Here, we synthesized a library of covalently functionalized fluorescent polymeric NPs (F-PLNPs) to evaluate the role of surface charge on the acute inflammation and the localization in the lung. Guanidinium-, acetylated-, zwitterionic-, hydroxylated-, PEGylated-, carboxylated- and sulfated-F-PLNPs were synthesized from aminated-F-PLNP. The primary particle sizes were identical, but the hydrodynamic sizes ranged from 210 to 345 nm. Following surface functionalization, the F-PLNPs showed diverse zeta potentials from -41.2 to 31.0 mV, and each F-PLNP showed a single, narrow peak. Pharyngeal aspiration with these eight types of F-PLNPs into rats produced diverse acute lung inflammation, with zeta potentials of the F-PLNPs showing excellent correlation with acute pulmonary inflammation parameters including the percentage of polymorphonuclear leukocytes (R(2) = 0.90, p < 0.0001) and the levels of interleukin-1β (R(2) = 0.83, p < 0.0001) and of cytokine-induced neutrophil chemoattractant-3 (R(2) = 0.86, p < 0.0001). These results imply that surface charge is a key factor influencing lung inflammation by functionalized polymeric NPs, which further confirms and extends the surface charge paradigm that we reported for pristine metal oxide NPs. This demonstrates that the surface charge paradigm is a valuable tool to predict the toxicity of NPs.
authors.affiliation: a Lab of Toxicology, Department of Medicinal Biotechnology, College of Natural Resources and Life Science , Dong-A University , Busan , Republic of Korea .
authors.forename: Jeongeun
authors.initials: J
authors.lastname: Kim
authors.affiliation: b School of Chemistry, West Mains Road, University of Edinburgh , Edinburgh , UK , and.
authors.forename: Sunay V
authors.initials: SV
authors.lastname: Chankeshwara
authors.affiliation: b School of Chemistry, West Mains Road, University of Edinburgh , Edinburgh , UK , and.
authors.forename: Frank
authors.initials: F
authors.lastname: Thielbeer
authors.affiliation: a Lab of Toxicology, Department of Medicinal Biotechnology, College of Natural Resources and Life Science , Dong-A University , Busan , Republic of Korea .
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Jeong
authors.affiliation: c ELEGI/Colt Laboratory, Centre for Inflammation Research, University of Edinburgh , Edinburgh , UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
authors.affiliation: b School of Chemistry, West Mains Road, University of Edinburgh , Edinburgh , UK , and.
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
authors.affiliation: a Lab of Toxicology, Department of Medicinal Biotechnology, College of Natural Resources and Life Science , Dong-A University , Busan , Republic of Korea .
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis; D005260:Female; D005453:Fluorescence; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced*; D011137:Polystyrenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D016207:Cytokines; D011137:Polystyrenes
keywords: Acute lung inflammation; functional group; particle pathogenicity paradigm; pharyngeal aspiration; surface charge paradigm