Design of polyamines-grafted starches for nucleotide analogues delivery: in vitro evaluation of the anticancer activity

Nucleotide analogues are a therapeutic class really promising and currently used in clinic notably against viral infectious diseases and cancer.1 However, their therapeutic potential is often restricted by a poor stability in vivo, the induction of severe side effects and a limited passive intracellular diffusion due to their hydrophilicity.2 Polysaccharide-based polymers (e. g. starch) have considerable advantages including a lack of toxicity and absence of antigenicity.3–5 The aim of this study was to develop new cationic starches able to form complexes with nucleotide analogues: to protect them and increase their cell uptake. The material should demonstrate good biocompatibility and low cytotoxicity. Different oligoamines, (TREN, TEPA and spermine) were covalently grafted to starch : the resulting cationic starch derivatives were characterized (e.g. degree of modification) and compared in their properties to form polyplexes with ATP as a model nucleotide. Among the tested candidates, the formulation of starch-TEPA and ATP with a N/P ratio = 2 led to nanoparticles with a size of 429 nm, a PdI of 0.054 and a zeta potential of -9 mV. MTT and LDH assays on A549 cell line showed a low toxicity of this cationic starch. Confocal microscopy studies proved that the cell internalization was an incubation time and energy dependent process. Most important, starch-TEPA complexes with ddGTP (0.3 mg/mL) showed a significant biological activity on A549 cancer cells (> 90 %) compared to plain ddGTP (~ 21 %) at the same concentration, revealing a real promising system to deliver intracellularly nucleotide analogues

Self-assembly of peptide-based nanostructures: Synthesis and biological activity

Peptide-based nanostructures have received much attention in the field of drug targeting. In fact, peptides have many advantages such as simplicity of the structure, biocompatibility, and chemical diversity. Moreover, some peptides, which are called cell-penetrating peptides, can cross cellular membranes and carry small molecules, small interfering RNA, or viruses inside live cells. These molecules are often covalently or noncovalently linked to cargoes, thus forming amphiphilic conjugates that can self-assemble. Supramolecular nanostructures formed from peptides are used in nanomedicine as a carrier to protect a drug and to target cancer cells. This review explores aliphatic-chain–conjugated peptides and drug-conjugated peptides that can self-assemble. Special emphasis is placed on the synthesis procedure, nanostructure formation, and biological activity

Spatial Resolution of a Micromegas-TPC Using the Charge Dispersion Signal

The Time Projection Chamber (TPC) for the International Linear Collider will need to measure about 200 track points with a resolution close to 100 $\mu$m. A Micro Pattern Gas Detector (MPGD) readout TPC could achieve the desired resolution with existing techniques using sub-millimeter width pads at the expense of a large increase in the detector cost and complexity. We have recently applied a new MPGD readout concept of charge dispersion to a prototype GEM-TPC and demonstrated the feasibility of achieving good resolution with pads similar in width to the ones used for the proportional wire TPC. The charge dispersion studies were repeated with a Micromegas TPC amplification stage. We present here our first results on the Micromegas-TPC resolution with charge dispersion. The TPC resolution with the Micromegas readout is compared to our earlier GEM results and to the resolution expected from electron statistics and transverse diffusion in a gaseous TPC.Comment: 5 pages, 8 figures, to appar in the Proceedings of the 2005 International Linear Collider Workshop (LCWS05), Stanford, 18-22 March 200

Design of Polyamine-Grafted Starches for Nucleotide Analogue Delivery: In Vitro Evaluation of the Anticancer Activity

Nucleotide analogues are a therapeutic class that is very promising and currently used in clinics, notably against viral infectious diseases and cancer. However, their therapeutic potential is often restricted by a poor stability in vivo, the induction of severe side effects, and limited passive intracellular diffusion due to their hydrophilicity. Polysaccharide-based polymers (e.g., starch) have considerable advantages, including a lack of toxicity and the absence of antigenicity. The aim of this study was to develop new cationic starches able to form complexes with nucleotide analogues, thus protecting them and increasing their cell uptake. At the same time, the material should demonstrate good biocompatibility and low cytotoxicity. Different polyamines, (TREN, TEPA, and spermine) were grafted to starch to evaluate the impact of side-chain properties. The resulting cationic starch derivatives were characterized (e.g., degree of modification) and compared in their ability to form polyplexes with ATP as a model nucleotide. Among the tested candidates, the formulation of starch–TEPA and ATP with an N/P ratio of 2 led to nanoparticles with a size of 429 nm, a PdI of 0.054, and a ζ potential of −9 mV. MTT and LDH assays on A549 cell line showed low toxicity for this polymer. Confocal microscopy study proved that the cell internalization was an incubation-time- and energy-dependent process. Most important, starch–TEPA complexed with ddGTP showed significant biological activity on A549 cancer cells compared to that of plain ddGTP at the same concentration

Design of polyamines-grafted starches for nucleotide analogues delivery: in vitro evaluation of the anticancer activity

Nucleotide analogues are a therapeutic class really promising and currently used in clinic notably against viral infectious diseases and cancer. However, their therapeutic potential is often restricted by a poor stability in vivo, the induction of severe side effects and a limited passive intracellular diffusion due to their hydrophilicity. Polysaccharide-based polymers (e. g. starch) have considerable advantages including a lack of toxicity and absence of antigenicity. The aim of this study was to develop new cationic starches able to form complexes with nucleotide analogues: to protect them and increase their cell uptake. The material should demonstrate good biocompatibility and low cytotoxicity. Different oligoamines, (TREN, TEPA and spermine) were covalently grafted to starch: the resulting cationic starch derivatives were characterized (e.g. degree of modification) and compared in their properties to form polyplexes with ATP as a model nucleotide. Among the tested candidates, the formulation of starch-TEPA and ATP with a N/P ratio = 2 led to nanoparticles with a size of 429 nm, a PdI of 0.054 and a zeta potential of -9 mV. MTT and LDH assays on A549 cell line showed a low toxicity of this cationic starch. Confocal microscopy studies proved that the cell internalization was an incubation time and energy dependent process. Most important, starch-TEPA complexes with ddGTP (0.3 mg/mL) showed a significant biological activity on A549 cancer cells (> 90 %) compared to plain ddGTP (~ 21 %) at the same concentration, revealing a real promising system to deliver intracellularly nucleotide analogues

Progress on a spherical TPC for low energy neutrino detection

The new concept of the spherical TPC aims at relatively large target masses with low threshold and background, keeping an extremely simple and robust operation. Such a device would open the way to detect the neutrino-nucleus interaction, which, although a standard process, remains undetected due to the low energy of the neutrino-induced nuclear recoils. The progress in the development of the fist 1 m$^3$ prototype at Saclay is presented. Other physics goals of such a device could include supernova detection, low energy neutrino oscillations and study of non-standard properties of the neutrino, among others.Comment: 3 pages, talk given at the 9th Workshop on Topics in Astroparticle and Underground Physics, Zaragoza, September 10-1