Carla Prata - Academia.edu (original) (raw)

Papers by Carla Prata

Research paper thumbnail of Peptide-PEG amphiphiles as brief communication cytophobic coatings for mammalian and bacterial cells

Research paper thumbnail of Non-viral charge reversal vectors for pDNA delivery

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2006

A synthetic vector that transform from a cationic to an anionic lipid intracellularly is describe... more A synthetic vector that transform from a cationic to an anionic lipid intracellularly is described. This charge-reversal lipid was synthesized and characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using this synthetic vector compared to current cationic lipids.

Research paper thumbnail of Enzyme-triggered PEGylated siRNA-nanoparticles for controlled release of siRNA

Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research, 2014

A key goal of our recent research efforts has been to develop novel 'triggerable nanoparticle... more A key goal of our recent research efforts has been to develop novel 'triggerable nanoparticle' systems with real potential utility in vivo. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here we describe investigations into the use of enzymes to trigger RNAi-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumour-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated siRNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nu...

Research paper thumbnail of 537. Charge-Reversal Lipids for Gene Transfection

Molecular Therapy, 2006

Abstract One of the critical steps limiting the efficiency of non-viral gene delivery is the intr... more Abstract One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for ...

Research paper thumbnail of 536. Charge Switchable Helper Lipids for Gene Delivery

Molecular Therapy, 2006

The current gene delivery approaches in use include viral vectors, synthetic cationic vectors, or... more The current gene delivery approaches in use include viral vectors, synthetic cationic vectors, or physical methods such as electroporation or gene gun. Of these, synthetic cationic vectors offer the advantages of low toxicity, nonimmunogenicity, large nucleic acid payloads, and ease of synthesis; but suffer from low transfection activities. This low activity likely reflects inefficiencies in the overall transfection pathway that

Research paper thumbnail of Nucleoside phosphocholine amphiphile for in vitro DNA transfection

Molecular BioSystems, 2005

A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfec... more A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfection efficacy and low cytotoxicity is described. TEM, ethidium bromide displacement assays, agarose gel electrophoresis and SAXS studies support the formation of lipoplexes for the transfection of CHO cells.

Research paper thumbnail of Well-Defined Nanoparticles Formed by Hydrophobic Assembly of a Short and Polydisperse Random Terpolymer, Amphipol A8-35

Langmuir, 2006

Amphipols are short amphilic polymers designed for applications in membrane biochemistry and biop... more Amphipols are short amphilic polymers designed for applications in membrane biochemistry and biophysics and used, in particular, to stabilize membrane proteins in aqueous solutions. Amphipol A8-35 was obtained by modification of a short-chain parent polymer (poly(acrylic acid); PAA) with octyl-and isopropylamine, to yield an amphiphilic product with an average molar mass of 9-10 kg‚mol -1 (sodium salt form) and a polydispersity index of 2.0 to 3.1, depending on the source of PAA. The behavior of A8-35 in aqueous buffers was studied by size exclusion chromatography, static and dynamic light scattering, equilibrium and sedimentation velocity analytical ultracentrifugation, and small angle neutron scattering. Despite the variable length of the chains and the random distribution of hydrophobic groups along them, A8-35 self-organizes into well-defined assemblies. The data are best compatible with most of the polymer forming compact assemblies (particles) with a molar mass of ∼40 kg‚mol -1 , a radius of gyration of ∼2.4 nm, and a Stokes radius of ∼3.15 nm. Each particle contains, on average, four A8-35 macromolecules and 75-80 octyl chains. Neutron scattering reveals a sharp interface between the particles and water. A minor (∼0.1%) mass fraction of the material forms much larger aggregates, whose proportion may increase under certain conditions of preparation or handling, such as low pH. They can be removed by gel filtration. * Corresponding authors.

Research paper thumbnail of Charge-Reversal Amphiphiles for Gene Delivery

Journal of the American Chemical Society, 2004

For gene therapies, viral vectors (infection) are by far the most specific, efficient and effecti... more For gene therapies, viral vectors (infection) are by far the most specific, efficient and effective means of DNA delivery, due to highly evolved, and specialized, viral proteins and peptides. However, enthusiasm for viral-vector mediated DNA delivery, unfortunately, has been tempered by growing concerns over the drug carriers --viral vectors. Non-viral vectors, on the other hand, have much better safety profiles although they are still generally inferior to most viral vectors. A hybrid system that combines both viral and non-viral advantages may overcome the major barriers to DNA delivery safely and efficiently.

Research paper thumbnail of Brief Communication Peptide-PEG Amphiphiles as Cytophobic Coatings for Mammalian and Bacterial Cells

Research paper thumbnail of A new dihydroxysterol from the marine phytoplankton Diacronema sp

Research paper thumbnail of Recent advances in amino acid analysis by capillary electromigration methods, 2011-2013

ELECTROPHORESIS, 2014

Amino acids are studied extensively using capillary electrophoresis. In this review we will repor... more Amino acids are studied extensively using capillary electrophoresis. In this review we will report the different researchs which have been done in the literature since 1998. We will describe the developments of, detection methods, separations of enantiomers, the new medical applications, and amino acids in food and plants.

Research paper thumbnail of Peptide-PEG Amphiphiles as Cytophobic Coatings for Mammalian and Bacterial Cells

Chemistry & Biology, 2006

Amphiphilic macromolecules containing a polystyrene-adherent peptide domain and a cell-repellent ... more Amphiphilic macromolecules containing a polystyrene-adherent peptide domain and a cell-repellent poly(ethylene glycol) domain were designed, synthesized, and evaluated as a cytophobic surface coating. Such cytophobic, or cell-repellent, coatings are of interest for varied medical and biotechnological applications. The composition of the polystyrene binding peptide domain was identified using an M13 phage display library. ELISA and atomic force spectroscopy were used to evaluate the binding affinity of the amphiphile peptide domain to polystyrene. When coated onto polystyrene, the amphiphile reduced cell adhesion of two distinct mammalian cell lines and pathogenic Staphylococcus aureus strains.

Research paper thumbnail of Supramolecular assemblies of DNA with neutral nucleoside amphiphiles

Chemical Communications, 2005

A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show tha... more A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-amphiphile supramolecular assemblies on a mica surface.

Research paper thumbnail of Dendritic supramolecular assemblies for drug delivery

Chemical Communications, 2005

Dendritic Supramolecular Assemblies for Drug Delivery -Preparation of assemblies of a dendritic m... more Dendritic Supramolecular Assemblies for Drug Delivery -Preparation of assemblies of a dendritic macromolecule with Reichardt's dye and the anticancer drug 10-hydroxycamptothecin, resp., in water are described. -(MORGAN, M. T.; CARNAHAN, M. A.; FINKELSTEIN, S.; PRATA, C. A. H.; DEGORICIJA, L.; LEE, S.

Research paper thumbnail of A new helper phospholipid for gene delivery

Chemical Communications, 2008

Research paper thumbnail of Enzyme-Triggered PEGylated pDNA-Nanoparticles for Controlled Release of pDNA in Tumors

Bioconjugate Chemistry, 2013

Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the fo... more Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the formulation of pDNA-nanoparticles with a surface layer of stealth/biocompatibility polymer (usually poly(ethylene glycol) [PEG]). This PEG layer ensures the colloidal stability of pDNA-nanoparticles in biological fluids and minimizes nanoparticle interactions with the reticulo-endothelical system. Unfortunately, the presence of the PEG layer appears to contribute to a reduction in efficiency of functional delivery of pDNA once target cells are reached. For this reason, we have focused recent research efforts on "triggerable" nanoparticle systems. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here, we describe investigations into the potential use of enzymes to trigger pDNA-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG 2000peptidyl lipids with peptidyl moieties sensitive to tumor-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated pDNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumor cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.

Research paper thumbnail of Cationic Nucleoside Lipids Based on a 3-Nitropyrrole Universal Base for siRNA Delivery

Bioconjugate Chemistry, 2009

Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared from D-ribose u... more Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared from D-ribose using a straightforward chemical synthesis. Several studies including DLS, TEM and ethidium bromide (EthBr) assay demonstrated that these amphiphilic molecules form supramolecular organizations of nanometer size in aqueous solutions and are able to bind nucleic acids. siRNA knockdown experiments were performed with these nucleolipids and we observed protein knockdown activity similar to the siPORT NeoFX positive control. No significant cytotoxicity was found.

Research paper thumbnail of The Effect of Charge-Reversal Amphiphile Spacer Composition on DNA and siRNA Delivery

Bioconjugate Chemistry, 2010

A series of charge-reversal amphiphiles with different spacers separating the headgroup from the ... more A series of charge-reversal amphiphiles with different spacers separating the headgroup from the hydrophobic chains are described for delivery of DNA and siRNA. Among them, the amphiphiles possessing a glycine spacer (e.g., B-GlyGly) showed effective DNA transfection in CHO and NIH 3T3 cells, as well as siRNA gene knockdown in HepG2 and UASMC cells. Ethidium bromide quenching assays revealed that DNA was released the fastest from the lipoplex of B-GlyGly in the presence of esterase. Also, X-ray diffraction results indicated that the DNA was located between the adjacent lipid bilayers in the lipoplex of B-GlyGly. These distinct features appear to be required for high transfection activity.

Research paper thumbnail of Nucleic Acid Complexing Glycosyl Nucleoside-Based Amphiphile

Bioconjugate Chemistry, 2005

A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA bind... more A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA binding was prepared using a convenient four-step synthetic route. The nucleic acid binding capabilities of this amphiphile were investigated by UV-vis, quasi-elastic light scattering (QELS), transmission electronic microscopy (TEM), gel electrophoresis, 31P NMR, IR, and circular dichroism (CD). Amphiphile-nucleic acid complex formation is a consequence of the amphiphilic character of the molecule, phosphate-sugar, and nucleobase-nucleobase interactions. This work presents for the first time a glyco-nucleo-amphiphile capable of binding efficiently the nucleic acid double helix structure.

Research paper thumbnail of Synthesis, Characterization, and In Vitro Transfection Activity of Charge-Reversal Amphiphiles for DNA Delivery

Bioconjugate Chemistry, 2011

A series of charge-reversal lipids were synthesized that possess varying chain lengths and end fu... more A series of charge-reversal lipids were synthesized that possess varying chain lengths and end functionalities. These lipids were designed to bind and then release DNA based on a change in electrostatic interaction with DNA. Specifically, a cleavable ester linkage is located at the ends of the hydrocarbon chains. The DNA release from the amphiphile was tuned by altering the length and position of the ester linkage in the hydrophobic chains of the lipids through the preparation of five new amphiphiles. The amphiphiles and corresponding lipoplexes were characterized by DSC, TEM, and X-ray, as well as evaluated for DNA binding and DNA transfection. For one specific charge-reversal lipid, stable lipoplexes of approximately 550 nm were formed, and with this amphiphile, effective in vitro DNA transfection activities was observed.

Research paper thumbnail of Peptide-PEG amphiphiles as brief communication cytophobic coatings for mammalian and bacterial cells

Research paper thumbnail of Non-viral charge reversal vectors for pDNA delivery

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2006

A synthetic vector that transform from a cationic to an anionic lipid intracellularly is describe... more A synthetic vector that transform from a cationic to an anionic lipid intracellularly is described. This charge-reversal lipid was synthesized and characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using this synthetic vector compared to current cationic lipids.

Research paper thumbnail of Enzyme-triggered PEGylated siRNA-nanoparticles for controlled release of siRNA

Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research, 2014

A key goal of our recent research efforts has been to develop novel 'triggerable nanoparticle... more A key goal of our recent research efforts has been to develop novel 'triggerable nanoparticle' systems with real potential utility in vivo. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here we describe investigations into the use of enzymes to trigger RNAi-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumour-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated siRNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nu...

Research paper thumbnail of 537. Charge-Reversal Lipids for Gene Transfection

Molecular Therapy, 2006

Abstract One of the critical steps limiting the efficiency of non-viral gene delivery is the intr... more Abstract One of the critical steps limiting the efficiency of non-viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the cell for ...

Research paper thumbnail of 536. Charge Switchable Helper Lipids for Gene Delivery

Molecular Therapy, 2006

The current gene delivery approaches in use include viral vectors, synthetic cationic vectors, or... more The current gene delivery approaches in use include viral vectors, synthetic cationic vectors, or physical methods such as electroporation or gene gun. Of these, synthetic cationic vectors offer the advantages of low toxicity, nonimmunogenicity, large nucleic acid payloads, and ease of synthesis; but suffer from low transfection activities. This low activity likely reflects inefficiencies in the overall transfection pathway that

Research paper thumbnail of Nucleoside phosphocholine amphiphile for in vitro DNA transfection

Molecular BioSystems, 2005

A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfec... more A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfection efficacy and low cytotoxicity is described. TEM, ethidium bromide displacement assays, agarose gel electrophoresis and SAXS studies support the formation of lipoplexes for the transfection of CHO cells.

Research paper thumbnail of Well-Defined Nanoparticles Formed by Hydrophobic Assembly of a Short and Polydisperse Random Terpolymer, Amphipol A8-35

Langmuir, 2006

Amphipols are short amphilic polymers designed for applications in membrane biochemistry and biop... more Amphipols are short amphilic polymers designed for applications in membrane biochemistry and biophysics and used, in particular, to stabilize membrane proteins in aqueous solutions. Amphipol A8-35 was obtained by modification of a short-chain parent polymer (poly(acrylic acid); PAA) with octyl-and isopropylamine, to yield an amphiphilic product with an average molar mass of 9-10 kg‚mol -1 (sodium salt form) and a polydispersity index of 2.0 to 3.1, depending on the source of PAA. The behavior of A8-35 in aqueous buffers was studied by size exclusion chromatography, static and dynamic light scattering, equilibrium and sedimentation velocity analytical ultracentrifugation, and small angle neutron scattering. Despite the variable length of the chains and the random distribution of hydrophobic groups along them, A8-35 self-organizes into well-defined assemblies. The data are best compatible with most of the polymer forming compact assemblies (particles) with a molar mass of ∼40 kg‚mol -1 , a radius of gyration of ∼2.4 nm, and a Stokes radius of ∼3.15 nm. Each particle contains, on average, four A8-35 macromolecules and 75-80 octyl chains. Neutron scattering reveals a sharp interface between the particles and water. A minor (∼0.1%) mass fraction of the material forms much larger aggregates, whose proportion may increase under certain conditions of preparation or handling, such as low pH. They can be removed by gel filtration. * Corresponding authors.

Research paper thumbnail of Charge-Reversal Amphiphiles for Gene Delivery

Journal of the American Chemical Society, 2004

For gene therapies, viral vectors (infection) are by far the most specific, efficient and effecti... more For gene therapies, viral vectors (infection) are by far the most specific, efficient and effective means of DNA delivery, due to highly evolved, and specialized, viral proteins and peptides. However, enthusiasm for viral-vector mediated DNA delivery, unfortunately, has been tempered by growing concerns over the drug carriers --viral vectors. Non-viral vectors, on the other hand, have much better safety profiles although they are still generally inferior to most viral vectors. A hybrid system that combines both viral and non-viral advantages may overcome the major barriers to DNA delivery safely and efficiently.

Research paper thumbnail of Brief Communication Peptide-PEG Amphiphiles as Cytophobic Coatings for Mammalian and Bacterial Cells

Research paper thumbnail of A new dihydroxysterol from the marine phytoplankton Diacronema sp

Research paper thumbnail of Recent advances in amino acid analysis by capillary electromigration methods, 2011-2013

ELECTROPHORESIS, 2014

Amino acids are studied extensively using capillary electrophoresis. In this review we will repor... more Amino acids are studied extensively using capillary electrophoresis. In this review we will report the different researchs which have been done in the literature since 1998. We will describe the developments of, detection methods, separations of enantiomers, the new medical applications, and amino acids in food and plants.

Research paper thumbnail of Peptide-PEG Amphiphiles as Cytophobic Coatings for Mammalian and Bacterial Cells

Chemistry & Biology, 2006

Amphiphilic macromolecules containing a polystyrene-adherent peptide domain and a cell-repellent ... more Amphiphilic macromolecules containing a polystyrene-adherent peptide domain and a cell-repellent poly(ethylene glycol) domain were designed, synthesized, and evaluated as a cytophobic surface coating. Such cytophobic, or cell-repellent, coatings are of interest for varied medical and biotechnological applications. The composition of the polystyrene binding peptide domain was identified using an M13 phage display library. ELISA and atomic force spectroscopy were used to evaluate the binding affinity of the amphiphile peptide domain to polystyrene. When coated onto polystyrene, the amphiphile reduced cell adhesion of two distinct mammalian cell lines and pathogenic Staphylococcus aureus strains.

Research paper thumbnail of Supramolecular assemblies of DNA with neutral nucleoside amphiphiles

Chemical Communications, 2005

A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show tha... more A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-amphiphile supramolecular assemblies on a mica surface.

Research paper thumbnail of Dendritic supramolecular assemblies for drug delivery

Chemical Communications, 2005

Dendritic Supramolecular Assemblies for Drug Delivery -Preparation of assemblies of a dendritic m... more Dendritic Supramolecular Assemblies for Drug Delivery -Preparation of assemblies of a dendritic macromolecule with Reichardt's dye and the anticancer drug 10-hydroxycamptothecin, resp., in water are described. -(MORGAN, M. T.; CARNAHAN, M. A.; FINKELSTEIN, S.; PRATA, C. A. H.; DEGORICIJA, L.; LEE, S.

Research paper thumbnail of A new helper phospholipid for gene delivery

Chemical Communications, 2008

Research paper thumbnail of Enzyme-Triggered PEGylated pDNA-Nanoparticles for Controlled Release of pDNA in Tumors

Bioconjugate Chemistry, 2013

Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the fo... more Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the formulation of pDNA-nanoparticles with a surface layer of stealth/biocompatibility polymer (usually poly(ethylene glycol) [PEG]). This PEG layer ensures the colloidal stability of pDNA-nanoparticles in biological fluids and minimizes nanoparticle interactions with the reticulo-endothelical system. Unfortunately, the presence of the PEG layer appears to contribute to a reduction in efficiency of functional delivery of pDNA once target cells are reached. For this reason, we have focused recent research efforts on "triggerable" nanoparticle systems. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here, we describe investigations into the potential use of enzymes to trigger pDNA-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG 2000peptidyl lipids with peptidyl moieties sensitive to tumor-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated pDNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumor cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.

Research paper thumbnail of Cationic Nucleoside Lipids Based on a 3-Nitropyrrole Universal Base for siRNA Delivery

Bioconjugate Chemistry, 2009

Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared from D-ribose u... more Cationic nucleoside lipids based on a 3-nitropyrrole universal base were prepared from D-ribose using a straightforward chemical synthesis. Several studies including DLS, TEM and ethidium bromide (EthBr) assay demonstrated that these amphiphilic molecules form supramolecular organizations of nanometer size in aqueous solutions and are able to bind nucleic acids. siRNA knockdown experiments were performed with these nucleolipids and we observed protein knockdown activity similar to the siPORT NeoFX positive control. No significant cytotoxicity was found.

Research paper thumbnail of The Effect of Charge-Reversal Amphiphile Spacer Composition on DNA and siRNA Delivery

Bioconjugate Chemistry, 2010

A series of charge-reversal amphiphiles with different spacers separating the headgroup from the ... more A series of charge-reversal amphiphiles with different spacers separating the headgroup from the hydrophobic chains are described for delivery of DNA and siRNA. Among them, the amphiphiles possessing a glycine spacer (e.g., B-GlyGly) showed effective DNA transfection in CHO and NIH 3T3 cells, as well as siRNA gene knockdown in HepG2 and UASMC cells. Ethidium bromide quenching assays revealed that DNA was released the fastest from the lipoplex of B-GlyGly in the presence of esterase. Also, X-ray diffraction results indicated that the DNA was located between the adjacent lipid bilayers in the lipoplex of B-GlyGly. These distinct features appear to be required for high transfection activity.

Research paper thumbnail of Nucleic Acid Complexing Glycosyl Nucleoside-Based Amphiphile

Bioconjugate Chemistry, 2005

A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA bind... more A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA binding was prepared using a convenient four-step synthetic route. The nucleic acid binding capabilities of this amphiphile were investigated by UV-vis, quasi-elastic light scattering (QELS), transmission electronic microscopy (TEM), gel electrophoresis, 31P NMR, IR, and circular dichroism (CD). Amphiphile-nucleic acid complex formation is a consequence of the amphiphilic character of the molecule, phosphate-sugar, and nucleobase-nucleobase interactions. This work presents for the first time a glyco-nucleo-amphiphile capable of binding efficiently the nucleic acid double helix structure.

Research paper thumbnail of Synthesis, Characterization, and In Vitro Transfection Activity of Charge-Reversal Amphiphiles for DNA Delivery

Bioconjugate Chemistry, 2011

A series of charge-reversal lipids were synthesized that possess varying chain lengths and end fu... more A series of charge-reversal lipids were synthesized that possess varying chain lengths and end functionalities. These lipids were designed to bind and then release DNA based on a change in electrostatic interaction with DNA. Specifically, a cleavable ester linkage is located at the ends of the hydrocarbon chains. The DNA release from the amphiphile was tuned by altering the length and position of the ester linkage in the hydrophobic chains of the lipids through the preparation of five new amphiphiles. The amphiphiles and corresponding lipoplexes were characterized by DSC, TEM, and X-ray, as well as evaluated for DNA binding and DNA transfection. For one specific charge-reversal lipid, stable lipoplexes of approximately 550 nm were formed, and with this amphiphile, effective in vitro DNA transfection activities was observed.