Browsing by Subject "Cancer therapy"
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Item Open Access A microfluidics-assisted double-barreled nanobioconjugate synthesis ıntroducing aprotinin as a new moonlight nanocarrier protein: tested toward physiologically relevant 3d-spheroid models(American Chemical Society, 2024-04-02) Nazir, Faiqa; Munir, Iqra; Yeşilöz, GürkanProteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nanoplatforms with manipulable payload release profiles. Here, we report a novel anticancer nanodrug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Doxorubicin (Apr-Dox) nanobioconjugate was prepared via a single-step microfluidics coflow mixing technique, a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously, i.e., Apr-Dox in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release ability, this nanobioconjugate achieves superior bioperformances, including high cellular uptake, efficient tumor penetration, and accumulation into the acidic tumor microenvironment, besides inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nanobioconjugates has been observed and validated compared to the anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nanobioconjugates toward breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nanobioconjugate shows a high potential for targeted drug delivery via a natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy as both an antimetastatic and a drug-carrying agent.Item Open Access The antiproliferative effect of celecoxib loaded pNIPAM nanoparticles(2012) Bayyurt, B.; Hasirci V.The aim of this study was to design a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) nanoparticles (NPs). The model drug, Celecoxib, is a cyclooxygenase-2 inhibitor and has a great potential in chemoprevention and treatment of various cancer types, however, the clinical use is limited due to the side effects on the cardiovascular system which is most probably due to the high doses used in clinical applications. In this study, a novel nanoparticle preparation approach, nanoprecipitation, was used. The amount of crosslinker affected the size, encapsulation efficiency, loading and release rate of NPs. The antiproliferative effect of Celecoxib was tested on human osteosarcoma cells, Saos-2, and the nanoparticles were found to have cytotoxicity. Celecoxib loaded pNIPAM NPs had higher cytotoxicity and the cells treated with this formulation showed abnormal nuclear and cytoskeletal morphology indicating apoptosis. The nanoparticles were detected within the cytoplasm and their distribution differed depending on whether NP is loaded with Celecoxib or not. The drug delivery system developed in this study appears to have a potential as an antiproliferative tool in various applications such as prevention of restenosis or biofilm formation on biomaterials. © 2012 American Scientific Publishers. All rights reserved.Item Open Access Biosystems engineering of prokaryotes with tumor-killing capacities(Bentham Science Publishers Ltd., 2016) Kalyoncu, E.; Olmez, T. T.; Ozkan, A. D.; Sarioglu, O. F.Certain bacteria selectively attack tumor tissues and trigger tumor shrinkage by producing toxins and modulating the local immune system, but their clinical utility is limited because of the dangers posed by systemic infection. Genetic engineering can be used to minimize the risks associated with tumor-targeting pathogens, as well as to increase their efficiency in killing tumor cells. Advances in genetic circuit design have led to the development of bacterial strains with enhanced tumor-targeting capacities and the ability to secrete therapeutics, cytotoxic proteins and prodrug-cleaving enzymes, which allows their safe and effective use for cancer treatment. The present review details the recent advances in the design and application of these modified bacterial strains.Item Open Access Cucurbit[7]uril-capped hybrid conjugated oligomer-gold nanoparticles for combined photodynamic-photothermal therapy and cellular imaging(ACS, 2020) Özkan, Melis; Tunç, İ.; Midilli, Y.; Ortaç, Bülend; Tuncel, DönüşHerein, hybrid nanoparticles composed of a redemitting conjugated oligomer (COL) and gold nanoparticles (Au-NPs) were prepared through a one-pot synthetic method in which the oligomer acts as a reducing agent as well as a matrix to wrap the newly formed Au nanoparticles. These hybrid nanoparticles(COL-Au-NPs) exhibited photodynamic and photothermal activity against both Gram-positive and Gram-negative bacterial strains. They were also proven to possess high photostability and thermal reversibility. Dark cytotoxicity of COL-Au-NPs toward pathogens and mammalian breast cancer cells (MCF-7) reduced significantly upon complexation with cucurbit[7]uril while preserving their light-induced cytotoxic activity when irradiated with a 915 nm laser for photothermal therapy and white light for photodynamic therapy, respectively. Furthermore, these nanoparticles have cellular imaging capability because of their intrinsic fluorescence characteristics and can be used in image-guided therapy.Item Open Access Development of an aprotinin-based novel nano-bioconjugate utilizing microfluidics via 3D cancer spheroid models(2024-08) Nazir, FaiqaProteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nano-platforms with manipulable payload release profiles. Here, we announce a novel anti-cancer nano-drug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Dox orubicin (Apr-Dox) nano-bioconjugate was prepared via a single-step microfluidics co-flow mixing technique; a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously i.e., Apr-Dox in 1:11 ratio (aprotinin an anti-metastatic carrier drug and chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e. pH) drug release ability, this nanobioconjugate achieves superior bio-performances including high cellular uptake, efficient tumor penetration and accumulation into acidic tumor microenvironment, as well as inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nano-bioconjugate has been observed and validated compared to anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nano-bioconjugates towards breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nano-bioconjugate shows a high potential for targeted drug delivery via natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy both as an anti-metastatic and drug-carrying agent.Item Open Access Non-covalent functionalized SWNTs as delivery agents for novel Bodipy-based potential PDT sensitizers(2009) Erbas, S.; Gorgulu, A.; Kocakusakogullari, M.; Akkaya, E. U.Pyrenyl-functionalized distyryl-Bodipy sensitizer attached non-covalently to SWNTs was shown to generate singlet oxygen when excited at 660 nm with a red LED array; this work emphasizes the potential of SWNT as a viable alternative carrier of bioactive agents, including photodynamic therapy sensitizers. © 2009 The Royal Society of Chemistry.Item Embargo T cell and natural killer cell membrane-camouflaged nanoparticles for cancer and viral therapies(American Chemical Society, 2024-05-24) Özsoy, Fatma; Mohammed, Mahir; Jan, Nasrullah; Lülek, Elif; Ertaş, Yavuz NuriExtensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.