title: Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology.
abstract: Vertical arrays of nanostructures can provide access to the cell cytoplasma and probe intracellular molecules. Here, the simple combination of diamond nanoneedle arrays with centrifugation-induced supergravity is shown to efficiently deliver drugs and biomaterials into the cytosol within several minutes, negotiating the endocytososomal system. The potential influence of the technique on cell metabolism is thoroughly studied. By detecting the phosphorylated histone variant H2AX (pH2AX) in the nucleus, it is proved that the operating process will not lead to DNA double-strand breaks. However, the mechanical disruption can temporarily improve the permeability of the cell membranes. Nanoneedle treatment affects cell metabolism at multiple points. The treatment can slightly elevate the apoptotic signal in A549 cells and can significantly increase the production of reactive oxygen species (ROS) in cells, particularly if combined with anticancer drugs. Meanwhile, the activity of cytosolic glucose 6-phosphate dehydrogenase (G6PD) is also raised to counterbalance the elevated ROS content. A detected depolarization of the mitochondrial membrane potential suggests mitochondrial involvement in the intracellular redox reactions and cell apoptosis which are induced by diamond nanoneedle treatment. Overall this study provides a novel understanding on the intracellular delivery mediated by nanoneedles, especially the impact on cell physiology.
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Muk Fung
authors.initials: MF
authors.lastname: Yuen
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR.
authors.forename: Fujin
authors.initials: F
authors.lastname: Ai
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Peter K N
authors.initials: PK
authors.lastname: Yu
authors.affiliation: Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Forensic Sciences, Faculty of Life Sciences, University of Bradford, United Kingdom, BD7 1DP.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002468:Cell Physiological Phenomena / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D018130:Diamond / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*; D009339:Needles; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D017382:Reactive Oxygen Species; D018130:Diamond; D005954:Glucosephosphate Dehydrogenase
keywords: diamond nanoneedle arrays; glucose 6-phosphate dehydrogenase; intracellular delivery; mitochondrial membrane potential; reactive oxygen species