Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells

  title={Novel Biocompatible Cationic Copolymers Based on Polyaspartylhydrazide Being Potent as Gene Vector on Tumor Cells},
  author={Manfred Ogris and Arun Kumar Kotha and Nicole Tietze and Ernst Wagner and Fabio Salvatore Palumbo and Gaetano Giammona and Gennara Cavallaro},
  journal={Pharmaceutical Research},
IntroductionThe reaction between α,β-poly(aspartylhydrazide) (PAHy), a water soluble synthetic polymer and 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) produced copolymers bearing permanent positive charges (PAHy–CPTA) with molecular weight of 10 kDa and PAHy–CPTA copolymers differing in positive charge amount (18–58%) were chosen for biological investigations. Materials and methodsBiophysical properties of DNA/PAHy–CPTA polyplexes were evaluated in terms of DNA condensation, zeta… 
Novel degradable oligoethylenimine acrylate ester-based pseudodendrimers for in vitro and in vivo gene transfer
It is shown that pseudodendritic core characteristics as well as different surface modifications on the core influence DNA-binding ability, cytotoxicity and transfection efficiency, and HD O was better tolerated than LPEI, while transgene expression was more tumor-specific and much lower in all other investigated organs, especially in the lung.
Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy
In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs, and may therefore serve as an innovative future therapy for pulmonary carcinoma.
Hyperthermia-induced targeting of thermosensitive gene carriers to tumors.
Hyperthermia led to increased accumulation of thermosensitive polymer and aggregation of therMosensitive polyplexes in HT-treated tumors, resulting in up to 10-fold increased DNA deposition compared with non-HT-treated tumor.
Biodegradable nanogel based on all-trans retinoic acid/pullulan conjugate for anti-cancer drug delivery
In order to improve the anticancer effect of drug, we designed and prepared biodegradable nanogel based on all-trans retinoic acid (ATRA)/pullulan conjugate (PURA). The nanogels have 47.19–38.24 %
Studies on Efficiency and Toxicity of in vivo Delivery Systems for siRNA and plasmid DNA
This dissertation has used the therapeutically relevant RAN siRNA to influence the growth of subcutaneous Neuro2A tumors in an in vivo model and evaluated different biodegradable polymers, that had been established in the lab, for their efficiency and safety in in vivo application.
Low generation PAMAM dendrimer and CpG free plasmids allow targeted and extended transgene expression in tumors after systemic delivery.
Tail vein injection of PAMAM polyplexes into immune competent mice bearing subcutaneous, well vascularized murine neuroblastoma tumors (Neuro2A) led to predominant luciferase reporter gene expression in the tumor, and negligible transgene expression levels in other organs.
Biotechnology and Bioterrorism
Although the barriers to applying the advanced biotechnologies for nefarious purposes continue to drop, it must be realized that substantial expertise is required to perform RD expertise that is not available by far to most terrorist groups.
Adenovirus-derived vectors for prostate cancer gene therapy.
The state of the art and future prospects of gene therapy in prostate cancer are reviewed and areas where further developments are necessary are highlighted, with a focus on adenoviral vectors.


Novel Cationic Copolymers of a Polyasparthylhydrazide: Synthesis and Characterization
α,β-poly(asparthylhydrazide) (PAHy), a water soluble synthetic polymer, was functionalized by using EDCI chemistry with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTACl) obtaining PAHy-CPTA copolymers, which are able to bind, neutralize, and protect DNA against degradation by DNase II.
Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA.
To investigate the possibility of producing charge-neutral gene delivery complexes with extended, non-particulate structures, DNA was allowed to self-assemble with a series of hydrophilic cationic
alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers (PAHy-GTA): novel polymers with potential for DNA delivery.
The ability of the PAHy-GTA(b) derivative to mediate the transfection of HepG2 cells using the marker gene beta-galactosidase was studied and the optimum plasmid/polymer mass ratio was examined in comparison to LipofectACE, Lip ofectin and polyethylenimine.
In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis.
The magnitude of the cytotoxic effects of all polymers were found to be time- and concentration dependent and the molecular weight as well as the cationic charge density of the polycations were confirmed as key parameters for the interaction with the cell membranes and consequently the cell damage.
A new water-soluble synthetic polymer, α,β-polyasparthydrazide, as potential plasma expander and drug carrier
Abstract The reaction between a polysuccinimide (PSI) and hydrazine produces a water-soluble polymer α,β-polyasparthydrazide (PAHy). Tests of the polymer on laboratory animals established its
Degradable gene carriers based on oligomerized polyamines.
  • J. Kloeckner, E. Wagner, M. Ogris
  • Medicine, Chemistry
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2006
Within the library, oligoethylenimine (800 Da)-based polymers showed the highest gene transfer efficiencies and exceeded the golden standard linear polyethylenIMine (22 kDa) in terms of activity/toxicity profile.
The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells
Application of the small particles in more concentrated form and over extended periods of time improves transfection activity, and analysis of gene expression at the cellular level revealed that the differences in overall gene expression largely result from different intensities per expressing cell, while the difference in the percentage of expressing cells is less substantial.
Glycidyl methacrylate derivatization of ?,?-poly(N-hydroxyethyl)--aspartamide and ?,?-polyasparthydrazide
Abstract α,β-Poly(N-hydroxyethyl)- dl -aspartamide (PHEA) and α,β-polyasparthydrazide (PAHy) are two synthetic macromolecules having many potential applications in the field of biomedical sciences.
Methodologies for monitoring nanoparticle formation by self-assembly of DNA with poly(l-lysine).
Analysis by light scattering and loss of ethidium bromide fluorescence both showed poly(l-lysine) (pLL)/DNA nanoparticles form over the lysine/phosphate ratio range 0.6-1.0, which probably indicates that the first two assays monitor DNA collapse into particles, while the electrophoresis assay measures neutralization of the charge on DNA.
PEGylated DNA/transferrin–PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery
In tumor bearing mice, application of non-PEGylated complexes through the tail vein resulted in reporter gene expression in tail and lung, but severe toxicity was observed in some mice, while PEGylation of the complexes mediated reporter gene transfer to the tumor without significant toxicity.