Nanoconjugate

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Miqin Zhang - One of the best experts on this subject based on the ideXlab platform.

  • folic acid peg conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by mri
    Journal of Biomedical Materials Research Part A, 2006
    Co-Authors: Conroy Sun, Raymond W Sze, Miqin Zhang
    Abstract:

    We report the development and in vitro study of a Nanoconjugate serving as a targeted magnetic resonance imaging (MRI) contrast enhancement agent for detection of cancer cells overexpressing the folate receptor. The Nanoconjugate was synthesized by coating superparamagnetic iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG), followed by conjugation with folic acid (FA). The specificity of the Nanoconjugate targeting cancerous cells was demonstrated by comparative intracellular uptake of the Nanoconjugate and PEG-/dextran-coated nanoparticles by human adenocarcinoma HeLa cells. Preferential targeting to cancerous cells was studied by comparing the uptake of the Nanoconjugate by HeLa cells and by non-FR expressing osteosarcoma MG-63 cells. Uptake of the Nanoconjugate by HeLa cells after 4 h incubation was found to be a 12-fold higher than that of PEG- or dextran-coated nanoparticles as quantified by inductively coupled plasma spectroscopy. A significant negative contrast enhancement was observed with magnetic resonance (MR) phantom imaging for HeLa cells over MG-63 cells, when both were cultured with the Nanoconjugate. Specificity of the Nanoconjugate for folate receptors was also verified with a competitive inhibition assay, in which HeLa cells were incubated with both NP-PEG-FA and free FA. The bifunctional PEG used has amide linkages within the PEG chains that can form interchain hydrogen bonding, leading to improved stability of the PEG coating. Self-assembled PEG can be controlled at the molecular level and are suitable for nanoscale coatings.

  • folic acid peg conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by mri
    Journal of Biomedical Materials Research Part A, 2006
    Co-Authors: Miqin Zhang
    Abstract:

    We report the development and in vitro study of a Nanoconjugate serving as a targeted magnetic resonance imaging (MRI) contrast enhancement agent for detection of cancer cells overexpressing the folate receptor. The Nanoconjugate was synthesized by coating superparamagnetic iron oxide nanoparticles with covalently bound bifunctional poly(ethylene glycol) (PEG), followed by conjugation with folic acid (FA). The specificity of the Nanoconjugate targeting cancerous cells was demonstrated by comparative intracellular uptake of the Nanoconjugate and PEG-/dextran-coated nanoparticles by human adenocarcinoma HeLa cells. Preferential targeting to cancerous cells was studied by comparing the uptake of the Nanoconjugate by HeLa cells and by non-FR expressing osteosarcoma MG-63 cells. Uptake of the Nanoconjugate by HeLa cells after 4 h incubation was found to be a 12-fold higher than that of PEG- or dextran-coated nanoparticles as quantified by inductively coupled plasma spectroscopy. A significant negative contrast enhancement was observed with magnetic resonance (MR) phantom imaging for HeLa cells over MG-63 cells, when both were cultured with the Nanoconjugate. Specificity of the Nanoconjugate for folate receptors was also verified with a competitive inhibition assay, in which HeLa cells were incubated with both NP–PEG–FA and free FA. The bifunctional PEG used has amide linkages within the PEG chains that can form interchain hydrogen bonding, leading to improved stability of the PEG coating. Self-assembled PEG can be controlled at the molecular level and are suitable for nanoscale coatings. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

Tatjana Paunesku - One of the best experts on this subject based on the ideXlab platform.

  • Titantium Dioxide Nanoparticles Assembled by DNA Molecules Hybridization and Loading of DNA Interacting Proteins
    2015
    Co-Authors: Tatjana Paunesku, Vinayak P. Dravid, Eric M. B. Brown, Angela Babbo, Cecille Cruz, Mohamed Aslam, Gayle E. Woloschak
    Abstract:

    This work demonstrates the assembly of TiO2 nanoparticles with attached DNA oligonucleotides into a 3D mesh structure by allowing base pairing between oligonucleotides. A change of the ratio of DNA oligonucleotide molecules and TiO2 nanoparticles regulates the size of the mesh as characterized by UV-visible light spectra, transmission electron microscopy and atomic force microscopy images. This type of 3D mesh, based on TiO2-DNA oligonucleotide Nanoconjugates, can be used for studies of nanoparticle assemblies in material science, energy science related to dye-sensitized solar cells, environmental science as well as characterization of DNA interacting proteins in the field of molecular biology. As an example of one such assembly, proliferating cell nuclear antigen protein (PCNA) was cloned, its activity verified, and the protein was purified, loaded onto double strand DNA oligonucleotide-TiO2 Nanoconjugates, and imaged by atomic force microscopy. This type of approach may be used to sample and perhaps quantify and/or extract specific cellular proteins from complex cellular protein mixtures affinity based on their affinity for chosen DNA segments assembled into the 3D matrix. Keywords Titanium dioxide nanoparticles; DNA; PCNA protein; atomic force microscopy; transmission electron microscopy; assembly; agarose; Nanoconjugate 1

  • cytotoxicity and dna cleavage with core shell nanocomposites functionalized by a kh domain dna binding peptide
    Nanoscale, 2013
    Co-Authors: Remon Bazak, Jan Ressl, Sumita Raha, Beau Wanzer, Seddik Abdel Salam, Tatjana Paunesku, Caroline Doty, Samy Elwany, Gayle E. Woloschak
    Abstract:

    A Nanoconjugate was composed of metal oxide nanoparticles decorated with peptides and fluorescent dye and tested for DNA cleavage following UV light activation. The peptide design was based on a DNA binding domain, the so called KH domain of the hnRNPK protein. This “KH peptide” enabled cellular uptake of Nanoconjugates and their entry into cell nuclei. The control Nanoconjugate carried no peptide; it consisted only of the metal oxide nanoparticle prepared as Fe3O4@TiO2 nanocomposite and the fluorescent dye alizarin red S. These components of either construct are responsible for Nanoconjugate activation by UV light and the resultant production of reactive oxygen species (ROS). Production of ROS at different subcellular locations causes damage to different components of cells: only Nanoconjugates inside cell nuclei can be expected to cause DNA cleavage. Degradation of cellular DNA with KH peptide decorated Nanoconjugates exceeded the DNA damage obtained from control, no-peptide Nanoconjugate counterparts. Moreover, caspase activation and cell death were more extensive in the same cells.

  • labeling tio2 nanoparticles with dyes for optical fluorescence microscopy and determination of tio2 dna Nanoconjugate stability
    Small, 2009
    Co-Authors: Kenneth T Thurn, Tatjana Paunesku, Stefan Vogt, Barry Lai, Jorg Maser, Eric Brown, Raymond C Bergan, Mohammed Aslam, Vinayak P. Dravid, Gayle E. Woloschak
    Abstract:

    Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO2) nanoparticles. These nanoparticles, when electronically linked to single-stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents. By interacting with complementary target sequences in living cells, these photoinducible TiO2-DNA Nanoconjugates have the potential to cleave intracellular genomic DNA in a sequence specific and inducible manner. The Nanoconjugates also become detectable by magnetic resonance imaging with the addition of gadolinium Gd(III) contrast agents. Herein two approaches for labeling TiO2 nanoparticles and TiO2-DNA Nanoconjugates with optically fluorescent agents are described. This permits direct quantification of fluorescently labeled TiO2 nanoparticle uptake in a large population of living cells (>10(4) cells). X-ray fluorescence microscopy (XFM) is combined with fluorescent microscopy to determine the relative intracellular stability of the Nanoconjugates and used to quantify intracellular nanoparticles. Imaging the DNA component of the TiO2-DNA Nanoconjugate by fluorescent confocal microscopy within the same cell shows an overlap with the titanium signal as mapped by XFM. This strongly implies the intracellular integrity of the TiO2-DNA Nanoconjugates in malignant cells.

  • gadolinium conjugated tio2 dna oligonucleotide Nanoconjugates show prolonged intracellular retention period and t1 weighted contrast enhancement in magnetic resonance images
    Nanomedicine: Nanotechnology Biology and Medicine, 2008
    Co-Authors: Tatjana Paunesku, Stefan Vogt, Jorg Maser, Kenneth T Thurn, Tianyi Ke, Rohan Dharmakumar, Nicole Mascheri, Aiguo Wu, Barbara Szolckowalska, Andrew C Larson
    Abstract:

    Abstract Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these Nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in Nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone. Consequently, T1-weighted contrast enhancements were observed in cells treated with Nanoconjugates but not in cells treated by the contrast agent alone. This type of Nanoconjugate with increased retention time, Gd accumulation, and intracellular delivery may find its use in Gd neutron-capture cancer therapy.

  • Methods for assessing DNA hybridization of peptide nucleic acid-titanium dioxide Nanoconjugates.
    Analytical biochemistry, 2008
    Co-Authors: Eric Brown, Tatjana Paunesku, Kenneth T Thurn, Benjamin Haley, Jimmy Clark, Taisa Priester, Gayle E. Woloschak
    Abstract:

    We describe the synthesis of peptide nucleic acid (PNA)-titanium dioxide (TiO(2)) Nanoconjugates and several novel methods developed to investigate the DNA hybridization behaviors of these constructs. PNAs are synthetic DNA analogs resistant to degradation by cellular enzymes that hybridize to single-stranded DNA (ssDNA) with higher affinity than DNA oligonucleotides, invade double-stranded DNA (dsDNA), and form different PNA/DNA complexes. Previously, we developed a DNA-TiO(2) Nanoconjugate capable of hybridizing to target DNA intracellularly in a sequence-specific manner with the ability to cleave DNA when excited by electromagnetic radiation but susceptible to degradation that may lower its intracellular targeting efficiency and retention time. PNA-TiO(2) Nanoconjugates described in the current article hybridize to target ssDNA, oligonucleotide dsDNA, and supercoiled plasmid DNA under physiological-like ionic and temperature conditions, enabling rapid, inexpensive, sequence-specific concentration of nucleic acids in vitro. When modified by the addition of imaging agents or peptides, hybridization capabilities of PNA-TiO(2) Nanoconjugates are enhanced, providing essential benefits for numerous in vitro and in vivo applications. The series of experiments shown here could not be done with either TiO(2)-DNA Nanoconjugates or PNAs alone, and the novel methods developed will benefit studies of numerous other Nanoconjugate systems.

Chunmeng Sun - One of the best experts on this subject based on the ideXlab platform.

  • synthesis and characterization of hyaluronic acid platinum iv Nanoconjugate with enhanced antitumor response and reduced adverse effects
    RSC Advances, 2015
    Co-Authors: Xiang Ling, Yan Shen, Chunyang Zhao, Liping Huang, Qiyue Wang, Chunmeng Sun
    Abstract:

    A hyaluronic acid–platinum(IV) Nanoconjugate with a high drug loading capacity was developed to mitigate the side effects of platinum(II). Pt(IV), HA–EDA, and HA–EDA–Pt(IV) Nanoconjugates were investigated by 1H NMR, 13C NMR, FT-NIR, and DSC. Negatively charged polymer–drug conjugates were of a uniform size around 186.4 nm and spherical in shape. In vitro antiproliferation and in vivo apoptosis assays proved that the nanomedicine possessed high cytotoxicity towards cancer cells. The enhanced antitumor effect was attributed to HA receptor-mediated endocytosis. Nanoscale conjugates exhibited desirable blood compatibility and negligible stimulation to blood vessels. The systemic toxicity study showed that polymer–drug conjugates were much safer than the parent drug evidenced by biochemical and histological analyses. The concise design of the Nanoconjugate offers a simple way to overcome the toxicity and non-selectivity of cisplatin, which could improve therapeutical outcomes of platinum drugs in cancer therapy.

  • tumor targeting delivery of hyaluronic acid platinum iv Nanoconjugate to reduce toxicity and improve survival
    Polymer Chemistry, 2015
    Co-Authors: Xiang Ling, Yan Shen, Runing Sun, Mengze Zhang, Jinyin Mao, Jing Xing, Chunmeng Sun
    Abstract:

    Cisplatin, although promising in clinical use, is seriously limited by systemic side effects. Consequently, a stimuli-sensitive Pt(IV) pro-drug was synthesized and tethered to ethylenediamine modified hyaluronic acid to form a tumor-targeting HA-EDA–Pt(IV) Nanoconjugate with reduced adverse reactions and enhanced efficacy. The Nanoconjugate with adjustable Pt(IV) segments possessed satisfactory size and potential, exhibited spherical shapes and demonstrated sustained release of platinum species. Cell experiments confirmed that nanoscale conjugates selectively recognized the HA receptor, effectively penetrated the cell membrane and were finally reduced to active forms with persistent antitumor activity. Toxicological evaluation suggested that the nanomedicine significantly alleviated toxic side effects. Alterations of the pharmacokinetic profiles and parameters implied in vivo behavioral discrepancy after conjugation. Polymer–drug conjugates improved the life quality of mice bearing melanoma, prolonged survival, minimized organ toxicity and body weight loss. The favorable tumor-targeting effect was also verified by tissue distribution and in vivo imaging analysis. This HA-EDA–Pt(IV) Nanoconjugate is expected to overcome the bottleneck of present platinum drugs and holds great potential in clinical application for cancer therapy.

Gayle E. Woloschak - One of the best experts on this subject based on the ideXlab platform.

  • Titantium Dioxide Nanoparticles Assembled by DNA Molecules Hybridization and Loading of DNA Interacting Proteins
    2015
    Co-Authors: Tatjana Paunesku, Vinayak P. Dravid, Eric M. B. Brown, Angela Babbo, Cecille Cruz, Mohamed Aslam, Gayle E. Woloschak
    Abstract:

    This work demonstrates the assembly of TiO2 nanoparticles with attached DNA oligonucleotides into a 3D mesh structure by allowing base pairing between oligonucleotides. A change of the ratio of DNA oligonucleotide molecules and TiO2 nanoparticles regulates the size of the mesh as characterized by UV-visible light spectra, transmission electron microscopy and atomic force microscopy images. This type of 3D mesh, based on TiO2-DNA oligonucleotide Nanoconjugates, can be used for studies of nanoparticle assemblies in material science, energy science related to dye-sensitized solar cells, environmental science as well as characterization of DNA interacting proteins in the field of molecular biology. As an example of one such assembly, proliferating cell nuclear antigen protein (PCNA) was cloned, its activity verified, and the protein was purified, loaded onto double strand DNA oligonucleotide-TiO2 Nanoconjugates, and imaged by atomic force microscopy. This type of approach may be used to sample and perhaps quantify and/or extract specific cellular proteins from complex cellular protein mixtures affinity based on their affinity for chosen DNA segments assembled into the 3D matrix. Keywords Titanium dioxide nanoparticles; DNA; PCNA protein; atomic force microscopy; transmission electron microscopy; assembly; agarose; Nanoconjugate 1

  • cytotoxicity and dna cleavage with core shell nanocomposites functionalized by a kh domain dna binding peptide
    Nanoscale, 2013
    Co-Authors: Remon Bazak, Jan Ressl, Sumita Raha, Beau Wanzer, Seddik Abdel Salam, Tatjana Paunesku, Caroline Doty, Samy Elwany, Gayle E. Woloschak
    Abstract:

    A Nanoconjugate was composed of metal oxide nanoparticles decorated with peptides and fluorescent dye and tested for DNA cleavage following UV light activation. The peptide design was based on a DNA binding domain, the so called KH domain of the hnRNPK protein. This “KH peptide” enabled cellular uptake of Nanoconjugates and their entry into cell nuclei. The control Nanoconjugate carried no peptide; it consisted only of the metal oxide nanoparticle prepared as Fe3O4@TiO2 nanocomposite and the fluorescent dye alizarin red S. These components of either construct are responsible for Nanoconjugate activation by UV light and the resultant production of reactive oxygen species (ROS). Production of ROS at different subcellular locations causes damage to different components of cells: only Nanoconjugates inside cell nuclei can be expected to cause DNA cleavage. Degradation of cellular DNA with KH peptide decorated Nanoconjugates exceeded the DNA damage obtained from control, no-peptide Nanoconjugate counterparts. Moreover, caspase activation and cell death were more extensive in the same cells.

  • labeling tio2 nanoparticles with dyes for optical fluorescence microscopy and determination of tio2 dna Nanoconjugate stability
    Small, 2009
    Co-Authors: Kenneth T Thurn, Tatjana Paunesku, Stefan Vogt, Barry Lai, Jorg Maser, Eric Brown, Raymond C Bergan, Mohammed Aslam, Vinayak P. Dravid, Gayle E. Woloschak
    Abstract:

    Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO2) nanoparticles. These nanoparticles, when electronically linked to single-stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents. By interacting with complementary target sequences in living cells, these photoinducible TiO2-DNA Nanoconjugates have the potential to cleave intracellular genomic DNA in a sequence specific and inducible manner. The Nanoconjugates also become detectable by magnetic resonance imaging with the addition of gadolinium Gd(III) contrast agents. Herein two approaches for labeling TiO2 nanoparticles and TiO2-DNA Nanoconjugates with optically fluorescent agents are described. This permits direct quantification of fluorescently labeled TiO2 nanoparticle uptake in a large population of living cells (>10(4) cells). X-ray fluorescence microscopy (XFM) is combined with fluorescent microscopy to determine the relative intracellular stability of the Nanoconjugates and used to quantify intracellular nanoparticles. Imaging the DNA component of the TiO2-DNA Nanoconjugate by fluorescent confocal microscopy within the same cell shows an overlap with the titanium signal as mapped by XFM. This strongly implies the intracellular integrity of the TiO2-DNA Nanoconjugates in malignant cells.

  • Methods for assessing DNA hybridization of peptide nucleic acid-titanium dioxide Nanoconjugates.
    Analytical biochemistry, 2008
    Co-Authors: Eric Brown, Tatjana Paunesku, Kenneth T Thurn, Benjamin Haley, Jimmy Clark, Taisa Priester, Gayle E. Woloschak
    Abstract:

    We describe the synthesis of peptide nucleic acid (PNA)-titanium dioxide (TiO(2)) Nanoconjugates and several novel methods developed to investigate the DNA hybridization behaviors of these constructs. PNAs are synthetic DNA analogs resistant to degradation by cellular enzymes that hybridize to single-stranded DNA (ssDNA) with higher affinity than DNA oligonucleotides, invade double-stranded DNA (dsDNA), and form different PNA/DNA complexes. Previously, we developed a DNA-TiO(2) Nanoconjugate capable of hybridizing to target DNA intracellularly in a sequence-specific manner with the ability to cleave DNA when excited by electromagnetic radiation but susceptible to degradation that may lower its intracellular targeting efficiency and retention time. PNA-TiO(2) Nanoconjugates described in the current article hybridize to target ssDNA, oligonucleotide dsDNA, and supercoiled plasmid DNA under physiological-like ionic and temperature conditions, enabling rapid, inexpensive, sequence-specific concentration of nucleic acids in vitro. When modified by the addition of imaging agents or peptides, hybridization capabilities of PNA-TiO(2) Nanoconjugates are enhanced, providing essential benefits for numerous in vitro and in vivo applications. The series of experiments shown here could not be done with either TiO(2)-DNA Nanoconjugates or PNAs alone, and the novel methods developed will benefit studies of numerous other Nanoconjugate systems.

Kenneth T Thurn - One of the best experts on this subject based on the ideXlab platform.

  • labeling tio2 nanoparticles with dyes for optical fluorescence microscopy and determination of tio2 dna Nanoconjugate stability
    Small, 2009
    Co-Authors: Kenneth T Thurn, Tatjana Paunesku, Stefan Vogt, Barry Lai, Jorg Maser, Eric Brown, Raymond C Bergan, Mohammed Aslam, Vinayak P. Dravid, Gayle E. Woloschak
    Abstract:

    Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO2) nanoparticles. These nanoparticles, when electronically linked to single-stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents. By interacting with complementary target sequences in living cells, these photoinducible TiO2-DNA Nanoconjugates have the potential to cleave intracellular genomic DNA in a sequence specific and inducible manner. The Nanoconjugates also become detectable by magnetic resonance imaging with the addition of gadolinium Gd(III) contrast agents. Herein two approaches for labeling TiO2 nanoparticles and TiO2-DNA Nanoconjugates with optically fluorescent agents are described. This permits direct quantification of fluorescently labeled TiO2 nanoparticle uptake in a large population of living cells (>10(4) cells). X-ray fluorescence microscopy (XFM) is combined with fluorescent microscopy to determine the relative intracellular stability of the Nanoconjugates and used to quantify intracellular nanoparticles. Imaging the DNA component of the TiO2-DNA Nanoconjugate by fluorescent confocal microscopy within the same cell shows an overlap with the titanium signal as mapped by XFM. This strongly implies the intracellular integrity of the TiO2-DNA Nanoconjugates in malignant cells.

  • gadolinium conjugated tio2 dna oligonucleotide Nanoconjugates show prolonged intracellular retention period and t1 weighted contrast enhancement in magnetic resonance images
    Nanomedicine: Nanotechnology Biology and Medicine, 2008
    Co-Authors: Tatjana Paunesku, Stefan Vogt, Jorg Maser, Kenneth T Thurn, Tianyi Ke, Rohan Dharmakumar, Nicole Mascheri, Aiguo Wu, Barbara Szolckowalska, Andrew C Larson
    Abstract:

    Abstract Nanoconjugates composed of titanium dioxide (TiO 2 ) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection of cultured cancer cells with these Nanoconjugates showed them to be superior to the free contrast agent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in Nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone. Consequently, T1-weighted contrast enhancements were observed in cells treated with Nanoconjugates but not in cells treated by the contrast agent alone. This type of Nanoconjugate with increased retention time, Gd accumulation, and intracellular delivery may find its use in Gd neutron-capture cancer therapy.

  • Methods for assessing DNA hybridization of peptide nucleic acid-titanium dioxide Nanoconjugates.
    Analytical biochemistry, 2008
    Co-Authors: Eric Brown, Tatjana Paunesku, Kenneth T Thurn, Benjamin Haley, Jimmy Clark, Taisa Priester, Gayle E. Woloschak
    Abstract:

    We describe the synthesis of peptide nucleic acid (PNA)-titanium dioxide (TiO(2)) Nanoconjugates and several novel methods developed to investigate the DNA hybridization behaviors of these constructs. PNAs are synthetic DNA analogs resistant to degradation by cellular enzymes that hybridize to single-stranded DNA (ssDNA) with higher affinity than DNA oligonucleotides, invade double-stranded DNA (dsDNA), and form different PNA/DNA complexes. Previously, we developed a DNA-TiO(2) Nanoconjugate capable of hybridizing to target DNA intracellularly in a sequence-specific manner with the ability to cleave DNA when excited by electromagnetic radiation but susceptible to degradation that may lower its intracellular targeting efficiency and retention time. PNA-TiO(2) Nanoconjugates described in the current article hybridize to target ssDNA, oligonucleotide dsDNA, and supercoiled plasmid DNA under physiological-like ionic and temperature conditions, enabling rapid, inexpensive, sequence-specific concentration of nucleic acids in vitro. When modified by the addition of imaging agents or peptides, hybridization capabilities of PNA-TiO(2) Nanoconjugates are enhanced, providing essential benefits for numerous in vitro and in vivo applications. The series of experiments shown here could not be done with either TiO(2)-DNA Nanoconjugates or PNAs alone, and the novel methods developed will benefit studies of numerous other Nanoconjugate systems.

  • original article diagnosis gadolinium conjugated tio 2 dna oligonucleotide Nanoconjugates show prolonged intracellular retention period and t1 weighted contrast enhancement in magnetic resonance images
    2008
    Co-Authors: Tatjana Paunesku, Stefan Vogt, Barry Lai, Jorg Maser, Kenneth T Thurn, Rohan Dharmakumar, Nicole Mascheri, Barbara Szolckowalska, Andrew C Larson, Raymond C Bergan
    Abstract:

    Nanoconjugates composed of titanium dioxide (TiO2) nanoparticles, DNA oligonucleotides, and a gadolinium (Gd) contrast agent were synthesized for use in magnetic resonance imaging. Transfection ofculturedcancercellswiththeseNanoconjugatesshowedthemtobesuperiortothefreecontrastagent of the same formulation with regard to intracellular accumulation, retention, and subcellular localization. Our results have shown that 48 hours after treatment, the concentration of Gd in Nanoconjugate-treated cells was 1000-fold higher than in cells treated with contrast agent alone. Consequently,T1-weightedcontrast enhancementswere observedincellstreated withNanoconjugates but not in cells treated by the contrast agent alone. This type of Nanoconjugate with increased retention time,Gdaccumulation,andintracellulardeliverymayfinditsuseinGdneutron-capturecancertherapy.