Cationic polymeric gene delivery of β-glucuronidase for doxorubicin prodrug therapy

Fonseca, Maria José Vieira; Storm, Gert; Hennink, Wim E.; Gerritsen, Winald R.; Haisma, Hidde J.

doi:10.1002/(sici)1521-2254(199911/12)1:6<407::aid-jgm71>3.0.co;2-q

Cited by 21 publications

(10 citation statements)

References 25 publications

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“…At present, the ILPP system is being investigated in our laboratory for its efficiency to deliver genes to ovarian carcinoma cells for the purpose of gene -dependent enzyme prodrug therapy. 29 …”

Section: Resultssupporting

confidence: 52%

Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells

et al. 2001

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A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly( 2 -( dimethylethylamino )ethyl methacrylate ) ( p( DMAEMA ) ). p( DMAEMA ) -based polyplexes have been successfully used for the transfection of OVCAR -3 cells in vitro. However, these polyplexes were unable to transfect OVCAR -3 cells growing in the peritoneal cavity of nude mice after intraperitoneal administration, which could be ascribed to inactivation by components ( including hyaluronic acid ) present in the tumor ascitic fluid. The present work aimed at ( a ) protecting p( DMAEMA ) -based polyplexes against destabilization or inactivation by polyanions such as hyaluronic acid present in tumor ascitic fluid and ( b ) enhancing cellular uptake of the protected p( DMAEMA ) -based polyplexes by targeting with antibody Fab H fragments. To fulfill these requirements, we have developed a detergent removal method to coat polyplexes with anionic lipids. With this method, spherical particles of $125 nm, which were protected from destabilization by polyanions, were obtained. More importantly, the transfection efficiency of lipopolyplexes was unaffected in the presence of hyaluronic acid, indicating that lipid coating of polyplexes protects against destabilization by hyaluronic acid. By conjugating antibody Fab H fragments directed against the epithelial glycoprotein -2 to the lipidic surface of these lipopolyplexes, target cell ± specific transfection of OVCAR -3 cells could be obtained in vitro. Cancer Gene Therapy ( 2001 ) 8, 405 ± 413

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Section: Resultssupporting

confidence: 52%

Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells

et al. 2001

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“…After administration of the appropriate prodrug, the active drug molecule is released by this localized enzyme, resulting in a potential reduction in selectivity due to the diffusion and uptake of active drug into nontargeted bystander cells. An additional strategy, gene-directed enzyme prodrug therapy (GDEPT) (11), involves the delivery of a gene encoding for a foreign enzyme to a chosen site, and, after subsequent enzyme expression, a dose of prodrug results in the selective release of the parent drug. GDEPT provides a source of enzyme localized within a cell, therefore reducing the problem of reduced selectivity associated with the bystander effect, but it requires the development of gene-delivery vehicles appropriate to a particular cell type.…”

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confidence: 99%

LEAPT: Lectin-directed enzyme-activated prodrug therapy

Robinson

Charlton

Garnier

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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. We describe a bipartite drug-delivery system that exploits (i) endogenous carbohydrate-to-lectin binding to localize glycosylated enzyme conjugates to specific, predetermined cell types followed by (ii) administration of a prodrug activated by that predelivered enzyme at the desired site. The carbohydrate structure of an ␣-L-rhamnopyranosidase enzyme was specifically engineered through enzymatic deglycosylation and chemical reglycosylation. Combined in vivo and in vitro techniques (gamma scintigraphy, microautoradiography and confocal microscopy) determined organ and cellular localization and demonstrated successful activation of ␣-L-rhamnopyranoside prodrug. Ligand competition experiments revealed enhanced, specific localization by endocytosis and a strongly carbohydrate-dependent, 60-fold increase in selectivity toward target cell hepatocytes that generated a >30-fold increase (from 0.02 to 0.66 mg) in protein delivered. Furthermore, glycosylation engineering enhanced the serum-uptake rate and enzyme stability. This created enzyme activity (0.2 units in hepatocytes) for prodrug therapy, the target of which was switched simply by sugar-type alteration. The therapeutic effectiveness of lectin-directed enzymeactivated prodrug therapy was shown through the construction of the prodrug of doxorubicin, Rha-DOX, and its application to reduce tumor burden in a hepatocellular carcinoma (HepG2) disease model.

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“…These studies suggested that b-glucuronidase gene therapy using PDMA as a carrier system and DOX-GA3 as the pro-drug can be potentially applied to cancer gene therapy. 54,55 The copolymer of P(NIPAM-co-DMA-co-BMA), was synthesized and its in vitro gene-transfection efficiency at different incubation temperatures was evaluated. 56,57 The formation/dissociation control of complexes can be manipulated by changing temperatures, where the transfection efficiency was observed to increase by lowering the temperature.…”

Section: Physical Properties Of Thermo-and Ph-responsive Pdma-relatedmentioning

confidence: 99%

pH-Responsive polymers: synthesis, properties and applications

Ravi²,

2008

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pH-Responsive polymers are systems whose solubility, volume, and chain conformation can be manipulated by changes in pH, co-solvent, and electrolytes. This review summarizes recent developments covering synthesis, physicochemical properties, and applications in various disciplines. A variety of synthetic methodologies comprising of emulsion polymerization and living radical polymerization techniques are described, and some of their salient features are highlighted. Several polymeric systems, such as homopolymers, block copolymers, microgels, hydrogels and polymer brushes at interfaces are reviewed, where important characteristics that govern their behavior in solutions are described. Potential applications of these systems in controlled drug delivery, personal and home care, industrial coatings, biological and membrane science, viscosity modifiers, colloid stabilization, and water remediation, are discussed.

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Cationic polymeric gene delivery of β-glucuronidase for doxorubicin prodrug therapy

Cited by 21 publications

References 25 publications

Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells

Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells

LEAPT: Lectin-directed enzyme-activated prodrug therapy

pH-Responsive polymers: synthesis, properties and applications

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