title: Toxic effect of zinc nanoscale metal-organic frameworks on rat pheochromocytoma (PC12) cells in vitro.
abstract: Metal-organic frameworks (MOFs) possess unique properties desirable for delivery of drugs and gaseous therapeutics, but their uncharacterized interactions with cells raise increasing concerns of their safety in such biomedical applications. We evaluated the adverse effects of zinc nanoscale MOFs on the cell morphology, cytoskeleton, cell viability and expression of neurotrophin signaling pathway-associated GAP-43 protein in rat pheochromocytoma PC12 cells. At the concentration of 25 μg/ml, zinc MOFs did not significantly affect morphology, viability and membrane integrity of the cells. But at higher concentrations (over 100 μg/ml), MOFs exhibited a time- and concentration-dependent cytotoxicity, indicating their entry into the cells via endocytosis where they release Zn(2+) into the cytosol to cause increased intracellular concentration of Zn(2+). We demonstrated that the toxicity of MOFs was associated with a disrupted cellular zinc homeostasis and down-regulation of GAP-43 protein, which might be the underlying mechanism for the improved differentiation in PC12 cells. These findings highlight the importance of cytotoxic evaluation of the MOFs before their biomedical application.
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: paper_mail@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Baochun
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Health Economy Administration, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Winthrop University Hospital, Mineola, NY 11501, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D019922:GAP-43 Protein / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009942:Organometallic Compounds / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D015032:Zinc / Q000633:toxicity*
chemical_list: D019922:GAP-43 Protein; D009942:Organometallic Compounds; D020932:Nerve Growth Factor; D015032:Zinc
keywords: Biocompatibility; Cytotoxocity; Metal organic frameworks; PC-12 cells; Toxic effect