期刊
NANOTOXICOLOGY
卷 13, 期 7, 页码 990-1004出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17435390.2019.1621398
关键词
Gold nanoparticles (AuNPs); cytotoxicity; cellular uptake; in vitro permeability; hCMEC; D3
资金
- European Union (FEDER funds) [POCI/01/0145/FEDER/007728]
- FCT/MEC, Fundacao para a Ciencia e a Tecnologia and Ministerio da Educacao e Ciencia [UID/MULTI/04378/2013, PD/BD/109634/2015]
- Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement (DESignBIOtecHealth - New Technologies for three Health Challenges of Modern Societies: Diabetes, Drug Abuse and Kidney Diseases), through the European [NORTE-01-0145-FEDER-000024]
- Fundação para a Ciência e a Tecnologia [PD/BD/109634/2015] Funding Source: FCT
Gold nanoparticles (AuNPs) have biomedical application on imaging and due to increased optical performance, star-shaped AuNPs are of special interest. Because shape, size and capping greatly influence their toxicokinetics and toxicodynamics, a systematic multiparametric comparative study of the influence of these parameters on the cytotoxicity, internalization, and in vitro permeability was conducted in human Cerebral Microvascular Endothelial Cell line (hCMEC/D3), an in vitro model of the human blood-brain barrier (BBB). AuNPs of different size (14 nm and similar to 50 nm), shape (spheres and stars), and coating (11-mercaptoundecanoic acid or MUA and sodium citrate) were synthesized and fully characterized. The time- and concentration-dependent cytotoxic profile of the tested AuNPs differed for the different AuNPs. Generally, toxicity was greater for stars relative to sphere-shaped AuNPs, and citrate coating was more toxic than MUA. Regarding the influence of size, smaller-sized AuNPs were more cytotoxic when compared at the same Au concentration. However, when the concentration of AuNPs was expressed as the number of AuNPs/mL, a higher degree of cytotoxicity was noted for the larger x334;50 nm AuNPs. To understand the influence of size, shape and capping, a systematic study design, in which only one of the variables changes, is determinant for correct data interpretation. Considering the results herein presented, for the sake of comparison of differently-sized AuNPs, it is preferable to design the study based upon the number of nanoparticles, since at a fixed Au concentration the number of particles available to promote effect is higher for smaller-sized AuNPs. Cellular internalization also differed among the tested AuNPs; although all were unable to cross the in vitro BBB, the intracellularly accumulated AuNPs can induce cell damage and later compromise BBB integrity and permeability.
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