Kuantum noktacıklarının hücresel etkileşim ve sitotoksisitelerinin araştırılması

TÜBİTAK SBAG Proje01.05.201

Anticancer use of nanoparticles as nucleic acid carriers

Commonly used drugs can mainly be classified as protein-based drugs such as insulin and small-molecule chemicals such as aspirin (Acetylsalicylic Acid). Search for organic drug-like molecules with high efficacy and low side-effects revealed nucleic acids as potential drugs. siRNA and miRNAs are one of the negative regulators of gene expression controlling various fundamental biological processes such as cell proliferation, stem cell division, and apoptosis. They act either by altering the stability of the mRNA transcripts and/or blocking protein translation by ribosomes. During the last decade, RNA molecules (siRNA and miRNA) and DNA fragments that code for them (shRNA or miRNA genes) were analyzed in detail to reveal their potential as new generation drugs against cancer. Accumulating data on these drugs will be discussed in the light of recent advances about the usage of nano particles as nucleic acid drug carriers

Magnetic actuation of nanofluids with ferromagnetic particles

Electromagnetically actuated microflows are generated by using ferromagnetic nanofluids containing Fe2O3 based nanoparticles. Because of their magnetic properties these nanoparticles are able to response to a magnetic field imposed along a microchannel so that a microflow could be driven. Nanofluid samples were located inside a minichannel and were directed with a magnetic field, which was induced by a solenoid wrapped around the minichannel, to drive the flow inside the minichannel, where its flow rate was also recorded. The flow rate was measured as a function of the imposed magnetic field. The corresponding pressure drop to deliver the same flow rate with an ordinary pump along the same minichannel was estimated so that the potential of this system for acting as a micropump in microfluidic applications was revealed

Magnetic nanoparticle based nanofluid actuation with dynamic magnetic fields

Magnetic nanoparticle suspensions and their manipulation are becoming an alternative research line and have very important applications in the field of microfluidics such as microscale flow control in microfluidic circuits, actuation of fluids in microscale, and drug delivery mechanisms. In microscale, it is possible and beneficial to use magnetic fields as actuators of such nanofluids, where these fluids could move along a gradient of magnetic field so that a micropump without any moving parts could be generated with this technique. Thus, magnetically actuated nanofluids could have the potential to be used as an alternative micro pumping system. Actuation of ferrofluid plugs with a changing magnetic field has been extensively studied in the literature. However; the flow properties of ferrofluids are sparsely investigated when the ferrofluid itself is forced to continuously flow inside a channel. As an extension of previous studies, this study aims to investigate flows of magnetic nanoparticle based nanofluids by a generated magnetic field and to compare the efficiency of the resulting system. Lauric Acid coated Super Paramagnetic Iron Oxide (SPIO-LA) was used as the ferrofluid sample in the experiments to realise actuation. Significant flow rates up to 61.8 mu L/s at nominal maximum magnetic field strengths of 300mT were achieved in the experiments. Results suggest that nanofluids with magnetic nanoparticles merit more research efforts in micro pumping. Thus, magnetic actuation could be a significant alternative for more common techniques such as electromechanical, electrokinetic, and piezoelectric actuation

Implementation of a simplified method for actuation of ferrofluids

Abstract Magnetic actuation of ferrofluids is an emergent field that will open up new possibilities in various fields of engineering. The quality and topology of the magnetic field that is being utilized in such systems is determinant in terms of flow properties, flow rates and overall efficiency. Determining the optimal magnetic field topology to achieve the desired results, and determining the methods by which these magnetic fields are to be generated are central problems of obtaining the desired flow. A healthy comparison of various magnetic field topologies requires a varied set of examples from the most simplified to most sophisticated. Such comparisons are necessary to have a well grounded starting point. This study focuses on a particular pump design that employs a simplified magnetic field topology to obtain ferrofluid flow. The results of this paper such as flow and pressure difference are intended to form a baseline for future reference

A novel magnetomechanical pump to actuate ferrofluids in minichannels

An improvement in the current methods of ferrofluid actuation was presented in this paper. A novel magnetomechanical microfluidic pump design was implemented with a ferrofluid as the active working fluid. Obtained flow rates were comparable to previous results in this research line. It was also seen that the basic pump architecture, which the subject pump is based on, enables much more room for further development

Anticancer use of nanoparticles as nucleic acid carriers

Advances in nanotechnology opened up new horizons in the field of cancer research. Nanoparticles made of various organic and inorganic materials and with different optical, magnetic and physical characteristics have the potential to revolutionize the way we diagnose, treat and follow-up cancers. Importantly, designs that might allow tumor-specific targeting and lesser side effects may be produced. Nanoparticles may be tailored to carry conventional chemotherapeutics or new generation organic drugs. Currently, most of the drugs that are commonly used, are small chemical molecules targeting disease-related enzymes. Recent progress in RNA interference technologies showed that, even proteins that are considered to be "undruggable" by small chemical molecules, might be targeted by small RNAs for the purpose of curing diseases, including cancer. In fact, small RNAs such as siRNAs, shRNAs and miRNAs can drastically change cellular levels of almost any given disease-associated protein or protein group, resulting in a therapeutic effect. Gene therapy attempts were failing mainly due to delivery viral vector-related side effects. Biocompatible, non-toxic and efficient nanoparticle carriers raise new hopes for the gene therapy of cancer. In this review article, we discuss new advances in nucleic acid and especially RNA carrier nanoparticles, and summarize recent progress about their use in cancer therapy

Synthesis of stable gold nanoparticles using linear polyethyleneimines and catalysis of both anionic and cationic azo dye degradation

Reduction of auric acid with polyethyleneimine (PEI) provides a simple, low-cost alternative for the production of cationic gold nanoparticles (GNPs). However, linear PEI (lPEI) failed to produce small, colloidally stable GNPs, so far. Since lPEI is a polyelectrolyte, pH should be an important factor both in reduction and stabilization of GNPs and may be optimized to produce small and stable lPEI/GNPs. Cationic GNPs were produced by the direct reduction of auric acid in water with lPEI utilizing two different methods to dissolve the polymer: by protonation or at high temperature. The influence of pH on the particle formation and properties was studied over a wide pH range (3.5 to 10). The impacts of the PEI/Au mass ratio, polymer molecular weight (2.5 and 25 kDa) and post-synthetic pH on the particle properties were also studied. Best is to dissolve lPEI by protonation and to clean the GNPs via controlled centrifugal precipitation. The MW did not influence the hydrodynamic size, stability or particle shape, but low MW lPEI provided faceted particles. This simple one pot synthesis of small, stable cationic GNPs in water is a valuable, simple alternative for producing new cationic GNPs with even low molecular weight lPEI. Additionally, these GNPs were evaluated as catalysts in the degradation of methyl orange (MO) (anionic-zwitterionic) and methylene blue (MB) (cationic) azo dyes at different pH values. The fastest degradation of MO and MB was recorded at pH 7.5 and 3.5, respectively. Overall, this is a rare case where a single catalyst quickly and effectively catalyzes the degradation of both cationic and anionic dyes. This journal i

Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag2S quantum dots

Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor

Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles

Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such nanoparticles theranostic. Yet, commonly used cationic coatings for efficient delivery of such anionic cargos, results in significant toxicity limiting translation of the technology to the clinic. Here, we describe a highly biocompatible, small and non-cationic SPION-based theranostic nanoparticles as novel gene therapy agents. We propose for the first-time, the usage of the microRNA machinery RISC complex component Argonaute 2 (AGO2) protein as a microRNA stabilizing agent and a delivery vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked and fluorophore-tagged SPION nanoparticles were developed (SP-AH nanoparticles) and used as a carrier for an autophagy inhibitory microRNA, MIR376B. These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. Furthermore, combination of the chemotherapy agent cisplatin with MIR376B-loaded SP-AH nanoparticles increased the efficacy of the anti-cancer treatment both in vitro in cells and in vivo in the nude mice. Therefore, we propose that AGO2 protein conjugated SPIONs are a new class of theranostic nanoparticles and can be efficiently used as innovative, non-cationic, non-toxic gene therapy tools for targeted therapy of cancer