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Michael H. Nantz - One of the best experts on this subject based on the ideXlab platform.

  • Expedited Articles A Modular Lymphographic Magnetic Resonance Imaging Contrast Agent: Contrast Enhancement with DNA Transfection Potential
    2016
    Co-Authors: Erik R. Wisner, Kimberly L. Aho-sharon, Michael J. Bennett, Sharron G. Penn, Carlito B. Lebrilla, Michael H. Nantz
    Abstract:

    A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRI) efficacy has been examined by indirect magnetic resonance lymphography. A lipidic N,N′-dimethylethylenediamine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was confirmed using MALDI spectrometry. An equimolar mixture of the Gd-chelate lipid and a commercially available diyne-PE was formulated as a liposome suspension and irradiated with UV light prior to imaging experiments. Subcutaneous injection of the liposomal gadolinium agent and subsequent MRI of rabbit axillary and popliteal lymph nodes revealed significant contrast enhancement up to 4 h postinjection. To explore the possibility of imaging a DNA Transfection event, the gadolinium contrast mixture was formulated with the cationic Transfection lipid DOTAP and complexed with the reporter gene encoding luciferase. DNA Transfection studies on the NIH3T3 cell line confirmed the Transfection activity of the dual-purpose contrast agent and exemplified the potential toward development of an imaging and DNA delivery vehicle. Since the advent of magnetic resonance imaging (MRI) for medical diagnostics, there has been continue

  • Inductive electron-withdrawal from ammonium ion headgroups of cationic lipids and the influence on DNA Transfection
    Biochimica et Biophysica Acta, 1998
    Co-Authors: Michael H. Nantz, Ji Zhu, Kim L. Aho-sharon, Debora Lim, Kent L. Erickson
    Abstract:

    We have prepared a panel of lipidic ammonium tetrafluoroborate salts that contain trifluoromethyl, trichloromethyl, and methyl groups attached to the headgroup. 19F-NMR analyses of the cationic lipid panel revealed that the differences in electron-withdrawal from the ammonium ion headgroup accounted for differences in ion-pairing. Exchange of the tetrafluoroborate counterion by complexation to DNA-phosphate of a reporter gene enabled us to probe the influence of inductive electron-withdrawal in cationic lipid-mediated DNA Transfection. We tested the lipid panel for Transfection activity in two cell lines. The results indicate that the inductive effects of electron-withdrawing functionality diminish Transfection activity in modest (2-4-fold) increments. The present study suggests that the mechanism whereby poly(alcohol)- or poly(ether)-substituted headgroups improve DNA Transfection is not based on electronic activation of the ammonium ion.

  • A Modular Lymphographic Magnetic Resonance Imaging Contrast Agent: Contrast Enhancement with DNA Transfection Potential
    Journal of medicinal chemistry, 1997
    Co-Authors: Erik R. Wisner, Kimberly L. Aho-sharon, Michael J. Bennett, Sharron G. Penn, Carlito B. Lebrilla, Michael H. Nantz
    Abstract:

    A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRI) efficacy has been examined by indirect magnetic resonance lymphography. A lipidic N,N‘-dimethylethylenediamine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was confirmed using MALDI spectrometry. An equimolar mixture of the Gd−chelate lipid and a commercially available diyne-PE was formulated as a liposome suspension and irradiated with UV light prior to imaging experiments. Subcutaneous injection of the liposomal gadolinium agent and subsequent MRI of rabbit axillary and popliteal lymph nodes revealed significant contrast enhancement up to 4 h postinjection. To explore the possibility of imaging a DNA Transfection event, the gadolinium contrast mixture was formulated with the cationic Transfection lipid DOTAP and complexed with the reporter gene encoding luciferase. DNA Transfection studies on the NIH3T3 cell line confi...

Toyoki Kunitake - One of the best experts on this subject based on the ideXlab platform.

Patrick Midoux - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA Transfection in dendritic cells
    Journal of materials chemistry. B, 2017
    Co-Authors: Mathieu Berchel, Sohail Akhter, Wilfried Berthe, Cristine Gonçalves, Marine Dubuisson, Chantal Pichon, Paul-alain Jaffrès, Patrick Midoux
    Abstract:

    Cationic lipid/co-lipid combinations have been extensively explored in gene delivery as alternatives to viral vectors. To be established as a gold standard of chemical vectors, considerable improvement in their Transfection efficiency is however required. Herein, we report a simple procedure to synthesize new cationic lipids and co-lipids for the DNA Transfection of dendritic cells (DCs). Seven α-amino-lipophosphonates featuring two aza-heterocycles with protonable sites (imidazole or pyridine) were synthesized and used as co-lipids in liposomes with cationic lipids. For each liposome, the cationic lipid is either an imidazolium lipophosphoramidate (lipid 2) or an α-amino-lipophosphonate containing a basic tertiary aliphatic amine in the polar head group (lipid 3b). The cationic lipids either with new co-lipids or DOPE formed positively charged nano-sized stable liposomes that effectively interact with plasmid DNA (pDNA) to produce lipoplexes. Membrane fusion studies showed that α-amino-phosphonates featuring an imidazole moiety in the polar head group exhibited higher fusion at pH 5.5 than pH 7.4. This study suggests that the best formulations for the Transfection of DCs (based on the % transfected cells and the intensity of EGFP-based fluorescence) are lipid 2 associated with either 3a, 3d or DOPE and cationic lipid 3b formulated with 3a or DOPE as a helper lipid. Furthermore, lipid 3a could be used as an alternative to DOPE as a helper lipid. Overall, these results indicate that novel imidazole containing α-amino-phosphonates can serve as effective Transfection agents for DC-based vaccines.

  • Synthesis of α-amino-lipophosphonates as cationic lipids or co-lipids for DNA Transfection in dendritic cells
    Journal of materials chemistry‎ B, 2017
    Co-Authors: Mathieu Berchel, Sohail Akhter, Wilfried Berthe, Marine Dubuisson, Chantal Pichon, Paul-alain Jaffrès, Cristine Gonçalvez, Patrick Midoux
    Abstract:

    Cationic lipid/co-lipid combinations have been extensively explored in gene delivery as alternatives to viral vectors. To be established as a gold standard of chemical vectors, considerable improvement in their Transfection efficiency is however required. Herein, we report a simple procedure to synthesize new cationic and co-lipids for the DNA Transfection of dendritic cells (DCs). Seven α-amino-lipophosphonates featuring two aza-heterocycles with protonable sites (imidazole or pyridine) were synthesized and used as co-lipids in liposomes with cationic lipid. For each liposome, the cationic lipid is either the imidazolium lipophosphoramidate (Lipid 2) or α-amino-lipophosphonate containing basic tertiary aliphatic amine in the polar head group (Lipid 3b). The cationic lipids either with new co-lipids or DOPE formed positively charged nano-sized stable liposomes that effectively interact with plasmide DNA (pDNA) to produce lipoplexes. Membrane fusion studies showed that α-amino-phosphonates featuring imidazole moiety in the polar head group exhibited higher fusion at pH 5.5 than pH 7.4. This study suggests that the best formulations for the Transfection of DCs (based on the % transfected cells and the intensity of EGFP-based fluorescence) are Lipid 2 associated with either 3a, 3d or DOPE and the cationic lipid 3b formulated with 3a or DOPE as helper lipid. Furthermore, Lipid 3a could be used as an alternative to DOPE as a helper lipid. Overall, these results indicate that novel imidazole containing α-amino-phosphonates can serve as effective Transfection agents for the DC-based vaccines.

Erik R. Wisner - One of the best experts on this subject based on the ideXlab platform.

  • Expedited Articles A Modular Lymphographic Magnetic Resonance Imaging Contrast Agent: Contrast Enhancement with DNA Transfection Potential
    2016
    Co-Authors: Erik R. Wisner, Kimberly L. Aho-sharon, Michael J. Bennett, Sharron G. Penn, Carlito B. Lebrilla, Michael H. Nantz
    Abstract:

    A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRI) efficacy has been examined by indirect magnetic resonance lymphography. A lipidic N,N′-dimethylethylenediamine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was confirmed using MALDI spectrometry. An equimolar mixture of the Gd-chelate lipid and a commercially available diyne-PE was formulated as a liposome suspension and irradiated with UV light prior to imaging experiments. Subcutaneous injection of the liposomal gadolinium agent and subsequent MRI of rabbit axillary and popliteal lymph nodes revealed significant contrast enhancement up to 4 h postinjection. To explore the possibility of imaging a DNA Transfection event, the gadolinium contrast mixture was formulated with the cationic Transfection lipid DOTAP and complexed with the reporter gene encoding luciferase. DNA Transfection studies on the NIH3T3 cell line confirmed the Transfection activity of the dual-purpose contrast agent and exemplified the potential toward development of an imaging and DNA delivery vehicle. Since the advent of magnetic resonance imaging (MRI) for medical diagnostics, there has been continue

  • A Modular Lymphographic Magnetic Resonance Imaging Contrast Agent: Contrast Enhancement with DNA Transfection Potential
    Journal of medicinal chemistry, 1997
    Co-Authors: Erik R. Wisner, Kimberly L. Aho-sharon, Michael J. Bennett, Sharron G. Penn, Carlito B. Lebrilla, Michael H. Nantz
    Abstract:

    A gadolinium-chelated liposomal contrast agent has been prepared, and magnetic resonance imaging (MRI) efficacy has been examined by indirect magnetic resonance lymphography. A lipidic N,N‘-dimethylethylenediamine derivative (4) containing a 10,12-diyne-diacyl domain was treated with DTPA anhydride followed by GdCl3 complexation. The complex was confirmed using MALDI spectrometry. An equimolar mixture of the Gd−chelate lipid and a commercially available diyne-PE was formulated as a liposome suspension and irradiated with UV light prior to imaging experiments. Subcutaneous injection of the liposomal gadolinium agent and subsequent MRI of rabbit axillary and popliteal lymph nodes revealed significant contrast enhancement up to 4 h postinjection. To explore the possibility of imaging a DNA Transfection event, the gadolinium contrast mixture was formulated with the cationic Transfection lipid DOTAP and complexed with the reporter gene encoding luciferase. DNA Transfection studies on the NIH3T3 cell line confi...

Seema Agarwal - One of the best experts on this subject based on the ideXlab platform.

  • Degradable and biocompatible poly(N,N-dimethylaminoethyl methacrylate-co-caprolactone)s as DNA Transfection agents.
    Macromolecular bioscience, 2013
    Co-Authors: Yi Zhang, Achim Aigner, Seema Agarwal
    Abstract:

    This study describes the synthesis of a set of novel, degradable block copolymers for DNA Transfection, and analyzes their physicochemical and biological properties. PEO macro-azoinitiators are used for the free radical copolymerization of DMAEMA and MDO, resulting in a series of different quaternized or non-quaternized block copolymers. All of the polymers show little cytotoxicity and full degradability, and thus, based on their favorable properties, may represent promising vectors for in vivo applications. Marked differences in DNA complexation efficacies and biological activities are observed, and one of the poly(PEG-co-(MDO-co-DMAEMA))s is identified as optimal for DNA Transfection.

  • Design and Biophysical Characterization of Bioresponsive Degradable Poly(dimethylaminoethyl methacrylate) Based Polymers for In Vitro DNA Transfection
    Biomacromolecules, 2012
    Co-Authors: Yi Zhang, Mengyao Zheng, Thomas Kissel, Seema Agarwal
    Abstract:

    Water-soluble, degradable polymers based on poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with low cytotoxicity and good p-DNA Transfection efficiency are highlighted in this article. To solve the nondegradability issue of PDMAEMA, new polymers based on DMAEMA and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) for gene Transfection were synthesized. A poly(ethylene oxide) (PEO) azo-initiator was used as free-radical initiator. PEGylation was performed to improve water solubility and to reduce cytotoxicity of the polymers. The resulting polymers contain hydrolyzable ester linkages in the backbone and were soluble in water even with very high amounts of ester linkages. These degradable copolymers showed significantly less toxicity with a MTT assay using L929 cell lines and demonstrated promising DNA Transfection efficiency when compared with the gold standard poly(ethyleneimine). Bioresponsive properties of the corresponding quaternized DMAEMA based degradable polymers were also studied. Although the quaternized DMAEMA copolymers showed enhanced water solubility, they were inferior in gene Transfection and toxicity as compared to the unquaternized copolymers.