Heparin coated and 2-deoxy-d-glucose conjugated iron oxide nanoparticles for biologic applications /

Akpınar, Yeliz
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 progress in the synthesis of iron oxide nanoparticles with different shapes (flower, cube, spherical) and compositions show that the heating power of the magnetic material can be optimized for hyperthermia. Compared to the therapy of using chemotherapeutic agents or molecular-targeting therapeutic agents, an alternative antitumor approach can be proposed by considering tumor metabolism. The reason cancer is so fast growing is that the mitochondria have been deactivated, so the cells avoid apoptosis, as well as being able to grow in the absence of oxygen (glycolysis). Dichloroacetate (DCA) which is a pyruvate dehydrogenase kinase inhibitor, reverses this process, induces apoptosis, decreases proliferation, and inhibits tumor growth. However, therapeutically prohibitive high DCA doses are needed for tumor growth suppression. Thus, preparation of magnetic nanoparticles designed to carry pharmacologically relevant doses of DCA directly to the tumor site and enhance its effective cellular uptake may represent a more effective therapeutic option. In this study, flower, cubic and spherical shaped iron oxide nanoparticles, having high heating power that can be used in hyperthermia application were prepared. For inductive heating of magnetic nanoparticles, an induction device was designed. Hyperthermia studies was started by using spherical iron oxide nanoparticles. The surface of nanoparticles prepared was modified with heparin, a natural polymer and DKA was embedded into heparin layer. However, for effectively targeting mitochondria, triphenylphosphonium cation was incorporated to DKA through a biodegradable amide linkage before loading on to the nanoparticle. Finally nanoparticles was conjugated to 2-deoxy-D-glucose (2-DG) in order to transport the particles into the cells via glucose transformers present on the cell membranes. It needs to be stated that, besides DKA and hyperthermia, both heparin and 2-DG are known to play role in apoptosis process. Therefore these novel nanoparticles are expected to deliver their cargo directly to cancer cell and cause a cell death via apoptosis. The binding and uptake of nanoparticles, cytotoxicity and apoptosis were investigated using liver cancer cell line (HepG2). It is known that iron oxide nanoparticles are used as a contrast reagent in MRI systems. Consequently, these nanoparticles were also useful for monitoring the outcomes of the medical treatment by magnetic resonance imaging, MRI.


Investigation of in vitro cytotoxic effects of heparin coated iron oxide nanoparticles combined with tpp-dca on human hepatocellular carcinoma cell line HEPG2
Saraç, Başak Ezgi; Güray, Nülüfer Tülün; Volkan, Mürvet; Department of Biology (2018)
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 su...
The Preparation and characterization of dendrimer coated magnetic nanoparticles for targeted cancer therapy
Khodadust, Rouhollah; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2013)
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. This technology has enabled the development of particles with nano sizes that can be fabricated from a multitude of materials in a variety of compositions. These nanoparticles include; quantum dots (QDs), polymeric nanoparticles, gold nanoparticles, magnetic nanoparticles and dendrimeric nanoparticles. In first section of this study, superparamagnetic iron oxide nanoparticles were synthesized by coprecipitation ...
Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles
Rouhollah, Khodadust; Pelin, Mutlu; Serap, Yalcin; Gozde, Unsoy; Ufuk, Gunduz (Elsevier BV, 2013-06-01)
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different gen...
Modeling and Characterization of Nanomedicine Transport within Tumor Microenvironment across Scales
Akalın, Ali Aykut; Özçelikkale, Altuğ (2022-09-19)
Despite significant advances in recent decades, diagnosis and treatment of cancer remain to be a major challenge. Advances in nanotechnology have enabled numerous nanoparticle (NP) formulations for efficient delivery of drugs and diagnostic agents to the target tumor site. The size, shape, charge, and surface characteristics of so-called nanomedicine can be tuned to affect the interactions of the NP with the physiological environment [1]. However, design efforts to develop nanomedicine for efficient deliver...
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
Y. Akpınar, “Heparin coated and 2-deoxy-d-glucose conjugated iron oxide nanoparticles for biologic applications /,” Ph.D. - Doctoral Program, Middle East Technical University, 2017.