title: Role of surface charge in determining the biological effects of CdSe/ZnS quantum dots.
abstract: The growing potential of quantum dots (QDs) in biomedical applications has provoked the urgent need to thoroughly address their interaction with biological systems. However, only limited studies have been performed to explore the effects of surface charge on the biological behaviors of QDs. In the present study, three commercially available QDs with different surface coatings were used to systematically evaluate the effects of surface charge on the cellular uptake, cytotoxicity, and in vivo biodistribution of QDs. Our results demonstrated that charged QDs entered both cancer cells and macrophages more efficiently than neutral ones, while negative QDs internalized mostly. Upon entry into cells, QDs were localized in different subcellular compartments (eg, cytoplasm and lysosomes) depending on the surface charge. Interestingly, inconsistent with the result of internalization, positive QDs but not negative QDs exhibited severe cytotoxicity, which was likely due to their disruption of cell membrane integrity, and production of reactive oxygen species. Biodistribution studies demonstrated that negative and neutral QDs preferentially distributed in the liver and the spleen, whereas positive QDs mainly deposited in the kidney with obvious uptake in the brain. In general, surface charge plays crucial roles in determining the biological interactions of QDs.
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Qiyue
authors.initials: Q
authors.lastname: Xia
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China ; Laboratory of Non-Human Primate Disease Model Research, State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy. West China Hospital, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xiao
mesh_terms: D000818:Animals; D019187:Cadmium Compounds / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D045663:Quantum Dots / Q000737:chemistry* / Q000648:ultrastructure; D000067996:RAW 264.7 Cells; D018036:Selenium Compounds / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology*; D013499:Surface Properties; D014018:Tissue Distribution / Q000187:drug effects; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D019187:Cadmium Compounds; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; D007770:L-Lactate Dehydrogenase; C031238:zinc sulfide
keywords: biodistribution; cellular uptake; cytotoxicity; intracellular distribution; reactive oxygen species; uptake pathways