title: Functionalized quantum dots induce proinflammatory responses in vitro: the role of terminal functional group-associated endocytic pathways.
abstract: PEGylation has been applied as an effective strategy of surface functionalization to improve the stability and reduce non-specific binding of quantum dots (QDs). However, its effects on the proinflammatory properties of QDs and the underlying mechanism have not been well elucidated yet. Herein, the proinflammatory effects of PEGylated CdSe/ZnS QDs with an amphiphilic polymer coating (PEG-pQDs) were investigated in human pulmonary epithelial cells and macrophages by evaluating the cytokine/chemokine production. The results showed that the proinflammatory effects of PEG-pQDs were strongly associated with the functional groups (-COOH, -NH2, -OH, and -OCH3) at the end of PEG chain. COOH-PEG-pQDs demonstrated the most proinflammatory effects followed by NH2-PEG-pQDs and HO-PEG-pQDs with CH3O-PEG-pQDs exhibiting the least proinflammatory effects. The proinflammatory effects of PEG-pQDs relied on lipid raft- and class A scavenger receptor (SRA)-dependent endocytic pathways as well as the downstream NF-κB and MAPK signaling cascades. COOH-PEG-pQDs were selectively internalized by lipid raft- and SRA-mediated endocytosis, which consequently activated NF-κB signaling pathway. On the other hand, NH2-PEG-pQDs and HO-PEG-pQDs were mostly internalized via lipid raft-mediated endocytosis, thereby activating p38 MAPK/AP-1 signaling cascades. These data revealed a critical role of terminal functional group-associated endocytic pathways in the proinflammatory responses induced by PEGylated QDs in human pulmonary epithelial cells and macrophages.
authors.affiliation: Key Lab of Health Informatics of Chinese Academy of Sciences, Guangdong Key Laboratory of Nanomedicine, Shenzhen Innovative Pharmacology and Biotherapy Pre-clinical Test Public Service Platform, Shenzhen Institutes of Advance Technology, Chinese Academy of Science, PR China.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhang
authors.forename: Ningning
authors.initials: N
authors.lastname: Gao
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.forename: Zichao
authors.initials: Z
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Ce
authors.initials: C
authors.lastname: Wang
authors.forename: Lanlan
authors.initials: L
authors.lastname: Liu
authors.forename: Daiwen
authors.initials: D
authors.lastname: Pang
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
mesh_terms: D045744:Cell Line, Tumor; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D021962:Membrane Microdomains / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D045663:Quantum Dots / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases