The prominent research area in nanomedicine is drug delivery and targeting systems based on nanom... more The prominent research area in nanomedicine is drug delivery and targeting systems based on nanomaterials. An ideal drug delivery system should intelligently find the diseased tissue, accumulate drug carrying agents in this location and controllably release therapeutic molecules to this site. Among the efficient drug delivery systems, chitosan, a natural, biodegradable, biocompatible, bioadhesive polymer, is gaining attention in the pharmaceutical field for a wide range of drug delivery. Chitosan acts as a penetration enhancer by opening the tight epithelial junctions. Magnetic nanoparticles provide a magnetic targeting of the drugs to the diseased tissue. In this study, in situ synthesis method was used for the preparation of chitosan coated magnetic nanoparticles (CS MNPs), involving the co-precipitation of iron salts in the prescence of chitosan and tripolyphosphate. The CS MNPs synthesized through this method are monodispersed and their surface is uniformly coated with low molec...
ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7... more ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 ± 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.
In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation me... more In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyl-trimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. Gene silencing effect of Survivin siRNA loaded nanoparticles (NPs) were studied on Doxorubicin resistant MCF-7 cell lines. Consequently, Survivin siRNA were triggered cell death when delivered by G4 PAMAM dendrimer coated magnetic nanoparticles. Survivin siRNA loaded G4 MNPs facilitate to overcome
Dendrimers are a relatively novel class of polymers with a well-defined, three-dimensional struct... more Dendrimers are a relatively novel class of polymers with a well-defined, three-dimensional structure and they are widely studied for their applications in biology and medicine. The build up of functional groups, symmetry perfection, nanosize, and internal cavities makes them suitable for applications in drug delivery and cancer therapy. Dendrimer coated magnetic nanoparticles (DcMNP) are synthesized through different cycles or ''generations'' by adding branched monomers that react with the functional groups of the core of iron oxide. In this study, bare iron oxide nanoparticles were synthesized and coated with fourth generation of PAMAM (G 4 -DcMNP) to be used in Doxorubicin loading studies. Loading efficiencies of Doxorubicin was carried out in PBS (pH: 7.2), TES (pH: 7.5) and Acetate (pH: 5.0) buffers and in different drug (15 µg/ml and 30 µg/ml) concentrations. The loading efficiencies of 15 µg/ml Doxorubicin were %68, %19 and %9 in PBS, TES and Acetate buffers, r...
Biodegradable polymeric magnetic nanomaterials gained importance in biomedical and bioengineering... more Biodegradable polymeric magnetic nanomaterials gained importance in biomedical and bioengineering research such as drug targeting, tissue engineering, cancer diagnosis and therapy. Polyhydroxybutyrate (PHB) is a nontoxic, biodegradable, biocompatible polymer and hence is suitable for medical applications. In this study, the cytotoxic effect of PHB coated magnetic nanoparticles were compared on sensitive and doxorubicin resistant MCF-7 cells. Resistant MCF-7 cell line was generated by applying doxorubicin in dose increments to sensitive cells. The synthesized nonoparticles were tested for their cytotoxic effects onto both sensitive and resistant cells. Then, PHB coated nanoparticles were applied onto cell lines and their uptake by the cells were observed with light microscopy. Cytotoxicity of PHB coated magnetic nanoparticles was investigated by XTT cell proliferation assay. The results demonstrated that synthesized nanoparticles were successfully uptaken by the cells and they were n...
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance o... more X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far. The aim of this study was to investigate the association of XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNP), smoking and alcohol consumption with the risk of HNSCC in Turkish population and also to compare to these results with the ones from both Turkish and different populations in the literature. The frequencies of Arg194Trp and Arg399Gln SNPs were studied in 55 HNSCC and 69 healthy individuals. Genomic DNA was isolated from peripheral blood and SNP was genotyped by PCR-RFLP method. The genotype and alle...
The objective of this study was to develop and evaluate the anticancer activity and the safety of... more The objective of this study was to develop and evaluate the anticancer activity and the safety of a combinational drug delivery system using polyamidoamine (PAMAM) dendrimer-coated iron oxide nanoparticles for doxorubicin and poly I:C delivery in vitro. Dendrimer-coated magnetic nanoparticles (DcMNPs) are suitable for drug delivery system as nanocarriers with their following properties, such as surface functional groups, symmetry perfection, internal cavities, nano-size and magnetization. These nanoparticles could be targeted to the tumor site under a magnetic field since they have a magnetic core. DcMNPs were found as a convenient vehicle for targeted doxorubicin delivery in cancer therapy. Poly (I:C) binding on doxorubicin loaded DcMNPs (DcMNPs-Dox) was reported for the first time in the literature. It was also demonstrated that loading of doxorubicin into the cavities of DcMNPs increases the binding efficiency of poly (I:C) to the surface functional groups of dendrimer up to 10 t...
Targeted drug delivery is a promising alternative to overcome the limitations of classical chemot... more Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field. Among various materials, chitosan has a great importance as a pH sensitive, natural, biodegradable, biocompatible and bioadhesive polymer. The aim of this study was to obtain an effective targeted delivery system for Doxorubicin, using chitosan coated MNPs. Different sized CS MNPs were produced by in situ synthesis method. The anti-cancer agent Doxorubicin was loaded onto CS MNPs which were characterized previously. Doxorubicin loading was confirmed by FTIR. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Our results showed that the CS MNPs have pH responsive release characteristics. The cellular internalization of Doxorubicin loaded CS MNPs were visualized by fluorescent microscopy. Doxorubicin loaded CS MNPs are efficiently taken up by MCF-7 (MCF-7/S) and Doxorubicin resistant MCF-7 (MCF-7/1 μM) breast cancer cells, which increases the efficacy of drug and also maintains overcoming the resistance of Doxorubicin in MCF-7/Dox cells. Consequently, CS MNPs synthesized at various sizes can be effectively used for the pH dependent release of Doxorubicin in cancer cells. Results of this study can provide new insights in the development of pH responsive targeted drug delivery systems to overcome the side effects of conventional chemotherapy.
DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair ... more DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population. The frequencies of Thr241Met SNP were studied in 58 laryngeal cancer cases (SSC) and 67 healthy individuals. Genomic DNA was isolated from peripheral blood samples of both controls and laryngeal cancer cases. Thr241Met SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of Thr241Met polymorphism were not statistically significant between the laryngeal cancer and control groups. Carrying mutant allele was not associated with the risk of laryngeal cancer. On the other hand, smoking and chronic alcohol consumption were associated with the risk of laryngeal cancer but there is no association between Thr241Met, smoking and alcohol consumption in laryngeal cancer cases. These results indicate that Thr241Met polymorphism was not associated with the development of laryngeal cancer in Turkish population. However, it should be kept in mind that the association of a polymorphism with cancer susceptibility can differ due to several factors such as cancer type, selection criteria, ethnic differences and size of the studied population.
Gemcitabine is an anticancer drug used in the treatment of different cancer types, including panc... more Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure - stellate cells - simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. ... more 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 generations (G2 , G3 , G4 , and G7 ) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4 DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4 DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3 DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390-1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy.
ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7... more ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 ± 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.
ABSTRACT Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor... more ABSTRACT Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor cells. The immobilization of Poly (I:C) onto nanoparticles is important for the fabrication of targeted delivery systems. In this study, different generations of newly synthesized PAMAM dendron-coated magnetic nanoparticles (DcMNP) which can be targeted to the tumor site under magnetic field were efficiently loaded for the first time with Poly (I:C). Different generations of DcMNPs (G2, G3, G4, G5, G6, and G7) were synthesized. Poly (I:C) activation was achieved in the presence of EDC and 1-methylimidazole. Loading of Poly (I:C) onto DcMNPs was followed by agarose gel electrophoresis. Acidic reaction conditions were found as superior to basic and neutral for binding of Poly (I:C). In addition, having more functional groups at the surface, higher generations (G7, G6, and G5) of PAMAM DcMNPs were found more suitable as a delivery system for Poly (I:C). Further in vitro and in vivo analyses of Poly (I:C)/PAMAM magnetic nanoparticles may provide new opportunities for the selective targeting and killing of tumor cells.
ABSTRACT The poly(hydroxy-amide) [PHA] family of polymers possess not only high temperature stabi... more ABSTRACT The poly(hydroxy-amide) [PHA] family of polymers possess not only high temperature stability, but also form a more thermally stable polymer (polybenzoxazole) [PBO] during thermal decomposition. The synthesis occurs in solution at low temperature, preventing premature ring cyclization to PBO. The molecular structure was confirmed from 1H-, 13C-NMR, and elemental analysis. One drawback for the highly aromatic PHA is the lack of a softening temperature before the onset of ring closure to PBO. Thus, poly(methoxy-amide) [PMeOA] and random copolymers of PHA and PMeOA have been synthesized and characterized. From microcalorimetry, the peak heat release capacity values for the copolymers is typically higher than that of the pure PHA (while still much lower than most other polymers); however, differential scanning calorimetry (DSC) analysis has shown glass transition temperatures to as low as 151°C for the copolymers. Thermo-gravimetric analysis (TGA) displays a three-step degradation associated with two ring closures to PBO from PHA and PMeOA (with the release of small low-fuel molecules) and the thermal degradation of PBO. The magnitude of the weight loss associated with each step is dependant on the percent of PHA, PMeOA, and aliphatic content in the copolymer. TGA and DSC analysis of PMeOA films under isothermal conditions show degradation and demethylation (cyclization) occurring simultaneously above 300°C and FT-IR displays benzoxazole ring forming under the same condition. Fibers have been spun from the molten state of PMeOA using a Micro-compounder. Fibers spun at 320°C, with average diameter of 180 μm, show an ultimate tensile strength, elongation at break, and Young's modulus of 60 MPa, 2.2% and 3.6 GPa, respectively. Films were also made by spin-coating or solvent casting to observe the effect of cyclization on tensile properties. These films had an ultimate tensile strength and Young's modulus of 120 MPa and 3 GPa, respectively.
The prominent research area in nanomedicine is drug delivery and targeting systems based on nanom... more The prominent research area in nanomedicine is drug delivery and targeting systems based on nanomaterials. An ideal drug delivery system should intelligently find the diseased tissue, accumulate drug carrying agents in this location and controllably release therapeutic molecules to this site. Among the efficient drug delivery systems, chitosan, a natural, biodegradable, biocompatible, bioadhesive polymer, is gaining attention in the pharmaceutical field for a wide range of drug delivery. Chitosan acts as a penetration enhancer by opening the tight epithelial junctions. Magnetic nanoparticles provide a magnetic targeting of the drugs to the diseased tissue. In this study, in situ synthesis method was used for the preparation of chitosan coated magnetic nanoparticles (CS MNPs), involving the co-precipitation of iron salts in the prescence of chitosan and tripolyphosphate. The CS MNPs synthesized through this method are monodispersed and their surface is uniformly coated with low molec...
ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7... more ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 ± 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.
In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation me... more In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyl-trimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. Gene silencing effect of Survivin siRNA loaded nanoparticles (NPs) were studied on Doxorubicin resistant MCF-7 cell lines. Consequently, Survivin siRNA were triggered cell death when delivered by G4 PAMAM dendrimer coated magnetic nanoparticles. Survivin siRNA loaded G4 MNPs facilitate to overcome
Dendrimers are a relatively novel class of polymers with a well-defined, three-dimensional struct... more Dendrimers are a relatively novel class of polymers with a well-defined, three-dimensional structure and they are widely studied for their applications in biology and medicine. The build up of functional groups, symmetry perfection, nanosize, and internal cavities makes them suitable for applications in drug delivery and cancer therapy. Dendrimer coated magnetic nanoparticles (DcMNP) are synthesized through different cycles or ''generations'' by adding branched monomers that react with the functional groups of the core of iron oxide. In this study, bare iron oxide nanoparticles were synthesized and coated with fourth generation of PAMAM (G 4 -DcMNP) to be used in Doxorubicin loading studies. Loading efficiencies of Doxorubicin was carried out in PBS (pH: 7.2), TES (pH: 7.5) and Acetate (pH: 5.0) buffers and in different drug (15 µg/ml and 30 µg/ml) concentrations. The loading efficiencies of 15 µg/ml Doxorubicin were %68, %19 and %9 in PBS, TES and Acetate buffers, r...
Biodegradable polymeric magnetic nanomaterials gained importance in biomedical and bioengineering... more Biodegradable polymeric magnetic nanomaterials gained importance in biomedical and bioengineering research such as drug targeting, tissue engineering, cancer diagnosis and therapy. Polyhydroxybutyrate (PHB) is a nontoxic, biodegradable, biocompatible polymer and hence is suitable for medical applications. In this study, the cytotoxic effect of PHB coated magnetic nanoparticles were compared on sensitive and doxorubicin resistant MCF-7 cells. Resistant MCF-7 cell line was generated by applying doxorubicin in dose increments to sensitive cells. The synthesized nonoparticles were tested for their cytotoxic effects onto both sensitive and resistant cells. Then, PHB coated nanoparticles were applied onto cell lines and their uptake by the cells were observed with light microscopy. Cytotoxicity of PHB coated magnetic nanoparticles was investigated by XTT cell proliferation assay. The results demonstrated that synthesized nanoparticles were successfully uptaken by the cells and they were n...
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance o... more X-ray repair cross-complementing (XRCC1) is one of the most important genes for the maintenance of genomic integrity and protection of cells from DNA damage. Although tobacco and alcohol consumption are the major risk factors for the development of head and neck squamous cell carcinoma (HNSCC), sequence variation in XRCC1 gene may alter HNSCC susceptibility. Reports on the relationship between HNSCC and polymorphisms in XRCC1 gene have been inconsistent so far. The aim of this study was to investigate the association of XRCC1 Arg194Trp and Arg399Gln single nucleotide polymorphisms (SNP), smoking and alcohol consumption with the risk of HNSCC in Turkish population and also to compare to these results with the ones from both Turkish and different populations in the literature. The frequencies of Arg194Trp and Arg399Gln SNPs were studied in 55 HNSCC and 69 healthy individuals. Genomic DNA was isolated from peripheral blood and SNP was genotyped by PCR-RFLP method. The genotype and alle...
The objective of this study was to develop and evaluate the anticancer activity and the safety of... more The objective of this study was to develop and evaluate the anticancer activity and the safety of a combinational drug delivery system using polyamidoamine (PAMAM) dendrimer-coated iron oxide nanoparticles for doxorubicin and poly I:C delivery in vitro. Dendrimer-coated magnetic nanoparticles (DcMNPs) are suitable for drug delivery system as nanocarriers with their following properties, such as surface functional groups, symmetry perfection, internal cavities, nano-size and magnetization. These nanoparticles could be targeted to the tumor site under a magnetic field since they have a magnetic core. DcMNPs were found as a convenient vehicle for targeted doxorubicin delivery in cancer therapy. Poly (I:C) binding on doxorubicin loaded DcMNPs (DcMNPs-Dox) was reported for the first time in the literature. It was also demonstrated that loading of doxorubicin into the cavities of DcMNPs increases the binding efficiency of poly (I:C) to the surface functional groups of dendrimer up to 10 t...
Targeted drug delivery is a promising alternative to overcome the limitations of classical chemot... more Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field. Among various materials, chitosan has a great importance as a pH sensitive, natural, biodegradable, biocompatible and bioadhesive polymer. The aim of this study was to obtain an effective targeted delivery system for Doxorubicin, using chitosan coated MNPs. Different sized CS MNPs were produced by in situ synthesis method. The anti-cancer agent Doxorubicin was loaded onto CS MNPs which were characterized previously. Doxorubicin loading was confirmed by FTIR. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Our results showed that the CS MNPs have pH responsive release characteristics. The cellular internalization of Doxorubicin loaded CS MNPs were visualized by fluorescent microscopy. Doxorubicin loaded CS MNPs are efficiently taken up by MCF-7 (MCF-7/S) and Doxorubicin resistant MCF-7 (MCF-7/1 μM) breast cancer cells, which increases the efficacy of drug and also maintains overcoming the resistance of Doxorubicin in MCF-7/Dox cells. Consequently, CS MNPs synthesized at various sizes can be effectively used for the pH dependent release of Doxorubicin in cancer cells. Results of this study can provide new insights in the development of pH responsive targeted drug delivery systems to overcome the side effects of conventional chemotherapy.
DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair ... more DNA repair systems are essential for normal cell function. Genetic alterations in the DNA repair genes such as X-ray repair cross-complementing group 3 (XRCC3), can cause a change in protein activity which results in cancer susceptibility. The aim of this study was to investigate the association of XRCC3 Thr241Met single nucleotide polymorphism (SNP), smoking and alcohol consumption with the risk of laryngeal cancer in Turkish population. The frequencies of Thr241Met SNP were studied in 58 laryngeal cancer cases (SSC) and 67 healthy individuals. Genomic DNA was isolated from peripheral blood samples of both controls and laryngeal cancer cases. Thr241Met SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of Thr241Met polymorphism were not statistically significant between the laryngeal cancer and control groups. Carrying mutant allele was not associated with the risk of laryngeal cancer. On the other hand, smoking and chronic alcohol consumption were associated with the risk of laryngeal cancer but there is no association between Thr241Met, smoking and alcohol consumption in laryngeal cancer cases. These results indicate that Thr241Met polymorphism was not associated with the development of laryngeal cancer in Turkish population. However, it should be kept in mind that the association of a polymorphism with cancer susceptibility can differ due to several factors such as cancer type, selection criteria, ethnic differences and size of the studied population.
Gemcitabine is an anticancer drug used in the treatment of different cancer types, including panc... more Gemcitabine is an anticancer drug used in the treatment of different cancer types, including pancreatic ductal adenocarcinoma. The maximum tolerated dose in humans is restricted by its side effects on healty cells. Furthermore, the fibrotic stroma produced by the pancreatic stellate cells prevents effective delivery of chemotherapeutic agents providing a safe-haven for the cancer cells. This becomes more of a problem considering the short half-life of this drug. Magnetic nanoparticle-based targeted drug delivery systems are a promising alternative to overcome the limitations of classical chemotherapies. The aim of this study is to obtain an effective targeted delivery system for gemcitabine using magnetic nanoparticles (MNPs) and all-trans retinoic acid (ATRA). This dual approach targets the tumor cells and its infrastructure - stellate cells - simultaneously. Gemcitabine and ATRA were loaded onto the PAMAM dendrimer-coated magnetic nanoparticles (DcMNPs), which were synthesized and characterized previously. Drug loading and release characteristics, and stability of the nanoparticles were investigated. Gemcitabine and ATRA loaded MNPs are efficiently taken up by pancreatic cancer and stellate cells successfully targeting and eliminating both cells. Results of this study can provide new insights on pancreatic cancer therapy where tumor is seen as a system with its stroma insead of epithelial cells alone.
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. ... more 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 generations (G2 , G3 , G4 , and G7 ) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4 DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4 DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3 DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390-1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy.
ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7... more ABSTRACT This study focuses on the synthesis and characterization of different generations (G0–G7) of polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles (DcMNPs). In this study, superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation method. The synthesized nanoparticles were modified with aminopropyltrimethoxysilane for dendrimer coating. Aminosilane-modified MNPs were coated with PAMAM dendrimer. The characterization of synthesized nanoparticles was performed by X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering, and vibrating sample magnetometry (VSM) analyses. TEM images demonstrated that the DcMNPs have monodisperse size distribution with an average particle diameter of 16 ± 5 nm. DcMNPs were found to be superparamagnetic through VSM analysis. The synthesis, aminosilane modification, and dendrimer coating of iron oxide nanoparticles were validated by FTIR and XPS analyses. Cellular internalization of nanoparticles was studied by inverted light scattering microscopy, and cytotoxicity was determined by XTT analysis. Results demonstrated that the synthesized DcMNPs, with their functional groups, symmetry perfection, size distribution, improved magnetic properties, and nontoxic characteristics could be suitable nanocarriers for targeted cancer therapy upon loading with various anticancer agents.
ABSTRACT Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor... more ABSTRACT Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor cells. The immobilization of Poly (I:C) onto nanoparticles is important for the fabrication of targeted delivery systems. In this study, different generations of newly synthesized PAMAM dendron-coated magnetic nanoparticles (DcMNP) which can be targeted to the tumor site under magnetic field were efficiently loaded for the first time with Poly (I:C). Different generations of DcMNPs (G2, G3, G4, G5, G6, and G7) were synthesized. Poly (I:C) activation was achieved in the presence of EDC and 1-methylimidazole. Loading of Poly (I:C) onto DcMNPs was followed by agarose gel electrophoresis. Acidic reaction conditions were found as superior to basic and neutral for binding of Poly (I:C). In addition, having more functional groups at the surface, higher generations (G7, G6, and G5) of PAMAM DcMNPs were found more suitable as a delivery system for Poly (I:C). Further in vitro and in vivo analyses of Poly (I:C)/PAMAM magnetic nanoparticles may provide new opportunities for the selective targeting and killing of tumor cells.
ABSTRACT The poly(hydroxy-amide) [PHA] family of polymers possess not only high temperature stabi... more ABSTRACT The poly(hydroxy-amide) [PHA] family of polymers possess not only high temperature stability, but also form a more thermally stable polymer (polybenzoxazole) [PBO] during thermal decomposition. The synthesis occurs in solution at low temperature, preventing premature ring cyclization to PBO. The molecular structure was confirmed from 1H-, 13C-NMR, and elemental analysis. One drawback for the highly aromatic PHA is the lack of a softening temperature before the onset of ring closure to PBO. Thus, poly(methoxy-amide) [PMeOA] and random copolymers of PHA and PMeOA have been synthesized and characterized. From microcalorimetry, the peak heat release capacity values for the copolymers is typically higher than that of the pure PHA (while still much lower than most other polymers); however, differential scanning calorimetry (DSC) analysis has shown glass transition temperatures to as low as 151°C for the copolymers. Thermo-gravimetric analysis (TGA) displays a three-step degradation associated with two ring closures to PBO from PHA and PMeOA (with the release of small low-fuel molecules) and the thermal degradation of PBO. The magnitude of the weight loss associated with each step is dependant on the percent of PHA, PMeOA, and aliphatic content in the copolymer. TGA and DSC analysis of PMeOA films under isothermal conditions show degradation and demethylation (cyclization) occurring simultaneously above 300°C and FT-IR displays benzoxazole ring forming under the same condition. Fibers have been spun from the molten state of PMeOA using a Micro-compounder. Fibers spun at 320°C, with average diameter of 180 μm, show an ultimate tensile strength, elongation at break, and Young's modulus of 60 MPa, 2.2% and 3.6 GPa, respectively. Films were also made by spin-coating or solvent casting to observe the effect of cyclization on tensile properties. These films had an ultimate tensile strength and Young's modulus of 120 MPa and 3 GPa, respectively.
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