Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Investigation of in vitro cytotoxic effects of heparin coated iron oxide nanoparticles combined with tpp-dca on human hepatocellular carcinoma cell line HEPG2
Download
index.pdf
Date
2018
Author
Saraç, Başak Ezgi
Metadata
Show full item record
Item Usage Stats
71
views
25
downloads
Cite This
Nanotechnology in medicine involves the applications of nanoparticles and one of the rising field is cancer nanotechnology, which has been increasingly used in cancer diagnostics, imaging, and therapeutic drug delivery. The advantage of the use of the nanoparticles is that, they can be designed to be specific for tumor tissue. This allows increased drug delivery efficiency and reduced off-target toxicities. Iron oxide nanoparticles used in this study are smaller than 100 nm but still it gives an enhanced surface area for the delivery of drugs. Considering the tumor metabolism, targeted therapeutic agents are an alternative anti-tumor treatment which has wide potentials. In most cancer cells, fast growing is related to the disabled mitochondria and consequently cells resist to undergo apoptosis and able to grow in the absence of oxygen. Dichloroacetate (DCA) which is a pyruvate dehydrogenase kinase inhibitor, reverse this process, reduce proliferation and inhibit the tumor growth. However, the DCA dose required to show this effect is significantly high. In order to use a pharmacologically suitable dose, magnetic nanoparticles which can increase the cellular uptake of DCA can be a more efficient alternative. Therefore, in this study, iron oxide nanoparticles (Fe3O4) were first modified with heparin, Dichloroacetate (DCA) is placed inside the heparin layers and in order to use glucose channels, conjugated with 2-deoxy-D-glucose. Triphenlyphosphonium (TPP) was also added to induce the uptake by mitochondria. Internalization of nanoparticles, their cytotoxicity, effects on mitochondrial membrane potential and apoptotic pathways were further analyzed in human hepatocellular carcinoma cell line, HepG2. Uptake assays performed with naked nanoparticles, 1-layer heparin coated TPP-DCA conjugated 2-DG attached nanoparticles, and nanoparticles with 2-layer heparin coated TPP-DCA conjugated with or without 2-DG showed that, heparin coating and 2-DG conjugation significantly increased cellular uptake of particles. Cytotoxicity experiments showed that, tailored nanoparticles increased DCA delivery into cancer cells compared to commercially available Na-DCA drug even when it was conjugated to triphenylphosphonium (TPP). Apoptosis studies indicated that tailored nanoparticles drive cells to undergo apoptosis rather than necrosis. Also, they decreased mitochondrial membrane potential, shifting the hyperpolarization to depolarization indicating that, 2-layer heparin coated TPP-DCA conjugated 2-DG attached nanoparticles not only increased DCA delivery significantly, but also killed hepatocellular carcinoma, HepG2 cells through apoptosis.
Subject Keywords
Heparin.
,
Cell lines.
,
Ferric oxide.
,
Nanoparticles.
,
Liver
,
Drug delivery systems.
URI
http://etd.lib.metu.edu.tr/upload/12622238/index.pdf
https://hdl.handle.net/11511/27489
Collections
Graduate School of Natural and Applied Sciences, Thesis
Suggestions
OpenMETU
Core
Targeted delivery of CPG-oligodeoxynucleotide to breast cancer cells by poly-amidoamine dendrimer-modified magnetic nanoparticles
Taghavi Pourianazar, Negar; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2016)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis
Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016)
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
Biopolymer based micro/nanoparticles as drug carriers for the treatment of skin diseases
Eke, Gözde; Hasırcı, Vasıf Nejat; Hasırcı, Nesrin; Department of Micro and Nanotechnology (2011)
Controlled drug delivery systems are becoming increasingly interesting with the contribution of nanotechnology. In the case of transdermal applications the greatest limitation is the highly impermeable outermost layer of the skin, the stratum corneum. One promising method of controlled transdermal drug delivery of the skin therapeutics is the use of nanoparticles as carriers. Encapsulation of the drug, as opposed to classical topical application of creams or emulsions, allows the drug to diffuse into hair f...
Heparin coated and 2-deoxy-d-glucose conjugated iron oxide nanoparticles for biologic applications /
Akpınar, Yeliz; Özçubukçu, Salih; Department of Chemistry (2017)
Over the past decade, there has been an increasing interest in using nanotechnology for cancer therapy. Magnetic-based systems containing magnetic nanoparticles have gained popularity because of their unique ability to be used in magnetic resonance imaging, magnetic targeting, drug carrying and hyperthermia. The last one represents a novel therapeutic concept to cancer treatmentIn biomedical and clinical applications the most commonly used magnetic nanomaterials are the iron oxide nanoparticles. Current pro...
CpG oligodeoxynucleotide- loaded PAMAM dendrimer-coated magnetic nanoparticles promote apoptosis in breast cancer cells
Pourianazar, Negar Taghavi; Gündüz, Ufuk (2016-03-01)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
B. E. Saraç, “Investigation of in vitro cytotoxic effects of heparin coated iron oxide nanoparticles combined with tpp-dca on human hepatocellular carcinoma cell line HEPG2,” M.S. - Master of Science, Middle East Technical University, 2018.