Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluorescein labeled carbohydrate (Glyc) probes were synthesized as analytical tools for the study of cellular lectins, i.e. SiaLe(x)-PAA-flu, Sia2-PAA-flu, GlcNAc2-PAA-flu, LacNAc-PAA-flu and a number of similar ones, with PAA a soluble polyacrylamide carrier. The binding of SiaLe(x)-PAA-flu was assessed using CHO cells transfected with E-selectin, and the binding of Sia2-PAA-flu was assessed by COS cells transfected with siglec-9. In flow cytometry assays, the fluorescein probes demonstrated a specific binding to the lectin-transfected cells that was inhibited by unlabeled carbohydrate ligands. The intense binding of SiaLe(x)-PAA-3H to the E-selectin transfected cells and the lack of binding to both native and permeabilized control cells lead to the conclusion that the polyacrylamide carrier itself and the spacer arm connecting the carbohydrate moiety with PAA did not contribute anymore to the binding. Tumors were obtained from nude mice by injection of CHO E-selectin or mock transfected cells. The fluorescent SiaLe(x)-PAA-flu probe could bind to the tumor sections from E-selectin positive CHO cells, but not from the control ones. Thus, these probes can be used to reveal specifically the carbohydrate binding sites on cells in culture as well as cells in tissue sections. The use of the confocal spectral imaging technique with Glyc-PAA-flu probes offered the unique possibility to detect lectins in different cells, even when the level of lectin expression was rather low. The confocal mode of spectrum recording provided an analysis of the probe localization with 3D submicron resolution. The spectral analysis (as a constituent part of the confocal spectral imaging technique) enabled interfering signals of the probe and intrinsic cellular fluorescence to be accurately separated, the distribution of the probe to be revealed and its local concentration to be measured.
 ...
PMID:Fluorescent carbohydrate probes for cell lectins. 1160 44

A group of novel poly(amido amine) homo- and copolymers (PAAs) containing secondary and tertiary amine groups in their main chain and different structures in the bisacrylamide segments were synthesized and evaluated as non-viral gene delivery vectors. Among these, also the disulfide-containing cystaminebisacrylamide was employed as a (co)monomer, yielding PAAs with variable amounts of bioreducible disulfide linkages in the main chain. Michael addition the trifunctional 1-(2-aminoethyl) piperazine to equimolar amounts of the appropriate bis(acrylamide) yielded linear polymers as was elucidated by their (13)C NMR spectra. The polymers possess buffering capacities between pH 5.1 and pH 7.4 higher than branched polyethylenimine (pEI) and are able to efficiently condense DNA into nanosized (<150 nm) and positively charged complexes. Transfection experiments with COS-7 cells showed that polyplexes from PAAs with disulfide linkages give significant higher transfections than those from PAAs lacking the disulfide linkage, and XTT assays showed that these polymers are essentially non-toxic. Variation of the disulfide content revealed that polyplexes of PAA copolymers with appropriate disulfide content have largely improved biophysical properties, yielding enhanced levels of gene expression along with low toxicity. The results demonstrate that bioreducible poly(amido amine)s are a very promising class of polymers for safe and efficient gene delivery.
 ...
PMID:Linear poly(amido amine)s with secondary and tertiary amino groups and variable amounts of disulfide linkages: synthesis and in vitro gene transfer properties. 1707 46

A series of novel bioreducible poly(amido amine)s containing multiple disulfide linkages (SS-PAAs) were synthesized and evaluated as nonviral gene vectors. These linear SS-PAAs could be easily obtained by Michael-type polyaddition of various primary amines to the disulfide-containing cystamine bisacrylamide. The SS-PAA polymers are relatively stable in medium mimicking physiological conditions (pH 7.4, 150 mM PBS, 37 degrees C), but are rapidly degraded in the presence of 2.5 mM DTT, mimicking the intracellular reductive environment (pH 7.4, [R-SH] = 5 mM, 37 degrees C). The polymers efficiently condense DNA into nanoscaled (<200 nm) and positively charged (>+20 mV) polyplexes that are stable under neutral conditions but are rapidly destabilized in a reductive environment, as was revealed by both dynamic light scatting measurement and agarose gel assays. Moreover, most of the poly(amido amine)s possess buffer capacities in the pH range pH 7.4-5.1 that are even higher than polyethylenimine (pEI), a property that may favorably contribute to the endosomal escape of the polyplexes. Polyplexes of four of the seven SS-PAAs studied were able to transfect COS-7 cells in vitro with transfection efficiencies significantly higher than those of branched pEI, being one of the most effective polymeric gene carriers reported to date. Importantly, also in the presence of serum, a high level of gene expression could be observed when the incubation time was elongated from 1 h to 4 h. XTT assays showed that SS-PAAs and their polyplexes possess essentially no or only very low cytotoxicity at concentrations where the highest transfection activity is observed. The results indicate that bioreducible poly(amido amine)s have excellent properties for the development of highly potent and nontoxic polymeric gene carriers.
 ...
PMID:Novel bioreducible poly(amido amine)s for highly efficient gene delivery. 1722 66

Poly(amido amine) (SS-PAA) random and block copolymers having bioreducible disulfide bonds in the main chain and amino groups with distinctly different basicity in the side chain were designed and synthesized by Michael addition polymerization between N, N'-cystaminebisacrylamide (CBA) and two amine monomers, i.e., histamine (HIS) and 3-(dimethylamino)-1-propylamine (DMPA). Copolymers containing variable HIS/DMPA ratios show higher ability to bind DNA than p(CBA-HIS) homopolymer and condense DNA into the polyplexes with particle sizes (<150 nm) that are smaller than polyplexes of p(CBA-HIS) ( approximately 220 nm). The buffer capacities of the copolymers increase with increasing HIS/DMPA ratio. These copolymers are able to transfect COS-7 cells in vitro with efficiencies that increase with increasing HIS/DMPA ratio. The random and block copolymers at a HIS/DMPA ratio of 70/30 combines optimal DNA condensation capability and buffer capacity, thereby inducing higher transfection efficiency in the absence and presence of serum as compared to p(CBA-HIS) homopolymer. Moreover, random and block copolymers show a similar transfection capacity, but both have higher capacity than the physical mixtures of p(CBA-HIS) and p(CBA-DMPA) homopolymers. XTT assay reveals that the polyplexes of the SS-PAA copolymers have essentially low cytotoxicity when the highest transfection activity is observed.
 ...
PMID:Random and block copolymers of bioreducible poly(amido amine)s with high- and low-basicity amino groups: study of DNA condensation and buffer capacity on gene transfection. 1772 1

A new method to adjust the particle size of interpolymer complexes has been developed by introduction of host-guest interaction into the dilute aqueous solution of poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG). Because of the cooperative hydrogen-bonding interaction, PAA can form the interpolymer complexes with PEG. Putting beta-cyclodextrin (beta-CD) into dilute PAA/PEG aqueous solution, the competition between host-guest and hydrogen-bonding interactions happens. The beta-CD/PAA/PEG ternary systems have been well characterized by ultraviolet-visible absorption spectroscopy (UV-vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), diffusion NMR spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and solid-state (13)C NMR spectroscopy. The results indicate that the hydrophobic cavity of beta-CD is threaded by linear polymers so that the hydrophilicity of PAA/PEG interpolymer complexes is improved greatly. Adjusting the amounts of beta-CD, the particle size of the interpolymer complexes can be readily controlled. The low cytotoxicity of various beta-CD/PAA/PEG ternary complexes has been confirmed using the MTT assay in COS-7 cell line. Doxorubicin (DOX), an anticancer drug, has been encapsulated into the beta-CD/PAA/PEG ternary complexes. The DOX-loaded beta-CD/PAA/PEG ternary complexes have been analyzed by confocal laser scanning microscopy (CLSM), flow cytometry analysis, and the MTT assay against human cervical carcinoma cell (Hela). The results indicate that beta-CD/PAA/PEG ternary complexes with controlled particle size could be used as safe and promising drug carriers.
 ...
PMID:Controlling the particle size of interpolymer complexes through host-guest interaction for drug delivery. 2012 Dec 62

Redox-responsive hyperbranched poly(amido amine)s (PAAs) with tertiary amino cores and amine, poly(ethylene glycol) (PEG) and hydroxyl terminal groups were prepared for DNA delivery respectively. The DNA condensation capability of PAAs was investigated using gel electrophoresis, and the results showed that PAA terminated with 1-(2-aminoethyl)piperazine (AEPZ) (BAA) is the most efficient in binding plasmid DNA (pDNA). The diameter and zeta-potential of polyplexes from PAAs were characterized using dynamic light scattering (DLS), and the morphology of the polyplexes was obtained using atomic force microscopy (AFM). All the PAAs were able to condense pDNA into nanoparticles with diameters between 50 and 200 nm with a positive surface charge when the weight ratio of polymer/DNA was higher than 20. Glutathione (GSH)-induced DNA release from polyplexes and the buffering capability of PAAs were investigated as well. Cytotoxicity of PAAs and in vitro gene transfection of polyplexes were evaluated in HEK293, COS-7, MCF-7 and Hep G2 cell lines, respectively. The results reflect that PAAs show remarkably low or even no cytotoxicity, and that PAA with amino terminal groups mediates the most efficient gene transfection with the transfection efficiency comparable to that of 25 kDa polyethylenimine. Further the effects of the presence of buthionine sulfoximine (BSO) on the transfection efficiency and cytotoxicity of BAA polyplexes were investigated.
 ...
PMID:Redox-responsive hyperbranched poly(amido amine)s with tertiary amino cores for gene delivery. 2369 14

Dip-coated multilayered thin films of poly(amido amine)s (PAAs) and DNA have been developed to provide surfaces with cell-transfecting capabilities. Three types of PAAs, differing in side chain functional groups, were synthesized and characterized for their properties in forming multilayered structures with ultrasonicated calf thymus DNA (CTDNA) as model DNA. All three polymers display a multilayer build-up in linear profiles as demonstrated by UV spectroscopy. More highly charged side chains were found to provide the lowest deposition of DNA. Surface profiles of the obtained films were investigated by atomic force microscopy (AFM) and static water contact angle measurements to reveal complete surface coverage after at least four layer pair depositions, where alternating patterns of surface profiles were observed depending on whether the cationic polymer or the anionic DNA layer was on top. The stability of the formed surfaces was investigated in vitro under physiological and reductive conditions. Owing to the presence of disulfide bonds in the PAA main chain, the films were readily degraded in the presence of 1mM of DTT in vitro. Under non-reductive physiological conditions, two of the thicker films underwent thermodynamic rearrangement, which resulted in release of approximately half of the incorporated material within 1h, which was caused by the physiological salt concentration. Further, this unpacking phenomenon proved useful in transfecting COS-7 cells seeded on top of these multilayers containing functional plasmid DNA encoding for green fluorescence protein (GFP). Two out of the three different multilayers facilitated good COS-7 cell attachment, proliferation, and transfection in vitro within 2d ays of culture. Fluorescence staining further revealed the presence of DNA-containing released film material among cultured cells. The present work demonstrates the possibility of coating surfaces with thin films that are conveniently adjustable in thickness and amount of active agent to provide cell-transfecting functionality. In this manner transfection can be achieved by simply culturing cells on a multilayer-coated surface in their optimal culture condition (in the presence of serum) and without the need of removing the transfection agent to avoid cytotoxicity.
 ...
PMID:Multilayered thin films from poly(amido amine)s and DNA. 2593 Oct 19