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Intracellular ZnO Nanorods Conjugated with Protoporphyrin for Local Mediated Photochemistry and Efficient Treatment of Single Cancer Cell
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.ORCID iD: 0000-0001-6235-7038
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2010 (English)In: NANOSCALE RESEARCH LETTERS, ISSN 1931-7573, Vol. 5, no 10, 1669-1674 p.Article in journal (Refereed) Published
Abstract [en]

ZnO nanorods (NRs) with high surface area to volume ratio and biocompatibility is used as an efficient photosensitizer carrier system and at the same time providing intrinsic white light needed to achieve cancer cell necrosis. In this letter, ZnO nanorods used for the treatment of breast cancer cell (T47D) are presented. To adjust the sample for intracellular experiments, we have grown the ZnO nanorods on the tip of borosilicate glass capillaries (0.5 mu m diameter) by aqueous chemical growth technique. The grown ZnO nanorods were conjugated using protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO nanorods. Mechanism of cytotoxicity appears to involve the generation of singlet oxygen inside the cell. The novel findings of cell-localized toxicity indicate a potential application of PPDME-conjugated ZnO NRs in the necrosis of breast cancer cell within few minutes.

Place, publisher, year, edition, pages
Springer Science Business Media , 2010. Vol. 5, no 10, 1669-1674 p.
Keyword [en]
ZnO nanorods, Cancer cell necrosis, Photodynamic therapy, Protoporphyrin dimethyl ester
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-61180DOI: 10.1007/s11671-010-9693-zISI: 000283124800022PubMedID: 21076704OAI: oai:DiVA.org:liu-61180DiVA: diva2:360903
Available from: 2010-11-05 Created: 2010-11-05 Last updated: 2014-09-25
In thesis
1. Zinc Oxide Nanostructure Based Electrochemical Sensors and Drug Delivery to Intracellular Environments
Open this publication in new window or tab >>Zinc Oxide Nanostructure Based Electrochemical Sensors and Drug Delivery to Intracellular Environments
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nanoscale science and nanostructure engineering have well established in the fabrication of novel electrochemical biosensors with faster response and higher sensitivity than of planar sensor configurations. Moreover nanostructures are suggested and used as efficient carrier of photosensitizers for cancerous cell treatment. The semi-conductor zinc oxide (ZnO) nanostructures have attracted much interest because of its unique piezoelectric, polar semiconducting, large surface area, catalytic properties, and being biosafe and biocompatible combined with the easiness of growth. This implies that ZnO nanostructures have a wide range of applications in optoelectronics, sensors, transducers, energy conversion and medical sciences. The aim of this study is to highlight recent developments in materials and techniques for electrochemical biosensing, photodynamic therapy, design, operation, and fabrication. The sensors in this study were used to detect and monitor real changes of metal ions and glucose across human fat cells and frog cells using changes in the electrochemical potential at the interface to the intracellular microenvironments. This thesis relates specifically to “zinc oxide nanostructure based electrochemical sensors and drug delivery to intracellular environments” for biological, biochemical and chemical applications.

The first part of the thesis presents extra and intracellular studies on metal ions such as Ca2+, Mg2+, and Na+…..etc selectively sensed by using ZnO nanorods grown on the tip of a borosilicate glass capillary (0.7 μm in diameter) with the aim to produce proto-type electrochemical extra/intracellular biosensors. The single human adipocyte and frog oocyte cells were used to selectively measure the intracellular free metal ions concentration. To make the sensors selective for metal ions with sufficient selectivity and stability, plastic membrane coatings containing specific ionophores were applied. These functionalized ZnO nanorods sensors showed high sensitivity and good stability with linear electrochemical potential versus a wide metal ion concentration range of interest. The measured intracellular values were consistent with values reported in the literature. Furthermore we have successfully determined that the intracellular potassium (K+) concentration decrease is not obligatory for apoptosis. The aim of this study is to show the possibility of using K+ selective microelectrode to detect and monitor intracellular changes of K+ concentration during injection of various test solution and chemically induced apoptosis in Xenopus laevis oocytes parallel with electrophysiological measurements to verify the accuracy.

The second part, presents the calcium ion (Ca2+) detection using functionalized ZnO nanorods attached as an extended gate metal oxide semiconductor field effect transistor (MOSFET). The electrochemical response was coupled directly to the gate of a commercial MOSFET to study the I-V characterization. Here we verified that ZnO nanorods grown on any thin wire can be combined with conventional electronic component to produce a sensitive and selective biosensor.

In the third part, we have performed the experiment to determine glucose concentration intracellularly and in airway surface liquid (ASL) with functionalized ZnO nanorod-coated microelectrodes. In this study, the GOD enzyme was immobilised electrostatically, drawing on the fact that there is a large difference in the isoelectric points of ZnO and glucose oxidase. Insulin has been found to affect the glucose uptake in human adipocytes and frog Xenopus laevis. The large size of these cells makes it possible to microinject specific reagents that interrupt or activate signal transmission to glucose. The measured glucose concentration in human adipocytes or frog oocytes and ASL using our ZnO nanorod sensor was consistent with values of glucose concentration reported in the literature by using other indirect techniques.

The fourth and final part covers the application of ZnO nanorods to cancer cells for photodynamic therapy. The ZnO nanorods were conjugated with protoporphyrin for local mediated photochemistry and efficient treatment of a single cancer cell. The ZnO nanorods were used as an efficient photosensitizer carrier system and at the same time providing intrinsic white light to achieve necrosis of the cancer cell. Breast cancer cells were used to study the catalytic effect of ZnO for treatment. The grown ZnO nanorods were conjugated with protoporphyrin dimethyl ester (PPDME), which absorbs the light emitted by the ZnO nanorods and cause the cytotoxicity which appears to involve the generation of reactive singlet oxygen inside the cell.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 64 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1376
Keyword
ZnO nanorods, Intracellular electrochemical sensor, Functionalization, Metal ions, Glucose, Human Adipocytes, Frog Oocytes, Airway surface liquid
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-68856 (URN)978-91-7393-142-7 (ISBN)
Public defence
2011-09-02, K3, Kåkenhus, Campus Norrköping, Linköpings universitet, Norrköping, 10:15 (English)
Opponent
Supervisors
Available from: 2011-06-08 Created: 2011-06-08 Last updated: 2014-01-15Bibliographically approved
2. Device Fabrication and Photosensitizing Role of ZnO Nanostructures in Photodynamic Therapy of Cancer
Open this publication in new window or tab >>Device Fabrication and Photosensitizing Role of ZnO Nanostructures in Photodynamic Therapy of Cancer
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In nanoscience and nanotechnology, zinc oxide (ZnO) is gaining much research attention due to direct wide band gap (3.3 eV), large exciton binding energy (60 meV), and deep level defects emissions that cover the whole visible range. ZnO nanorods (NRs) in comparison to normal bio molecules and large surface area to volume ratio, allow them to interact within the cell thus are used as convincing intracellular carriers of photosensitizers. Vertical NRs are wave guiding cavities enhancing the light extraction efficiency from devices and are stable photosensitizing agents with their biophotonic, and biodegradation properties, therefore are appealing candidates for the photodynamic therapy of cancer.

The heterojunction LEDs of ZnO NRs/p-GaN are best choice to take the advantage of GaN ideal blue-light emission and fabricated LEDs explore the potential of white LEDs with superior performance. The main objective of this thesis is not only to fabricate ZnO NRs/p-GaN, or ZnO nanotubes (ZNTs)/p-GaN heterostructures, but also to investigate their optical properties for photodynamic therapy. These LEDs have showed enhanced EL intensity covering the visible band (425–750 nm).

ZnO nanorods are grown on the borosilicate glass capillaries (0.7 μm diameter) and then conjugated with photosensitizer. Such glass capillaries having ZnO nanorods complex with photosensitizer on them are used as pointer for intracellular mediated photochemistry in cells to achieve their necrosis. Mitochondrial staining of melanoma and foreskin fibroblast cells was done by Mitotracker Red with the aim of targeting the specific organelle with the prepared ZnO nanowires (NWs) Femtotip to see ROS production. Cytotoxic effects of nanometallic oxides e.g. ZnO-NRs, MnO2 NRs, and Fe2O3 NPs individually and their ligands with photosensitizers in osteosarcoma (U2OS) cells are also explored. Thus bare and ligands of nanometallic oxides, with particular focus of ZnO nanowires are having significant and convincing cytotoxic effects via the liberation of reactive oxygen species as well as Zn+2 ions in labeled cells, thus can be assigned as anticancer agents for breast cancer, melanoma cancer and osteosarcoma cells.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 56 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1392
Keyword
Zinc oxide nanostructures, light emitting diodes, reactive oxygen species, photosensitizer, cancer cell, photodynamic therapy
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-71319 (URN)978-91-7393-083-3 (ISBN)
Public defence
2011-10-21, K2, Kåkenhus, Campus Norrköping, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2011-10-11 Created: 2011-10-11 Last updated: 2014-01-15Bibliographically approved

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Sultana, KishwarAsif, MuhammadNour, OmerWillander, Magnus

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