Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes

Wetering, Petra van de; Cherng, Jong Yuh; Talsma, H.; Hennink, Wim E.

doi:10.1016/s0168-3659(97)00059-x

Cited by 241 publications

(230 citation statements)

References 26 publications

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“…These observations were in agreement with previously published results. 8,59 Transfection efficiency of P(DMAEMA-co-OEGMA) copolymer gene vectors was dependent on the N/P ratio and decreased gradually with increasing F OEGMA ( Figure 4A). In agreement with the results from pDNA binding, high N/P ratios (in the range of 10-40) were necessary to achieve high transfection levels.…”

Section: Resultsmentioning

confidence: 99%

“…This controlled radical polymerization technique allows synthesis of well-defined copolymers with predictable molecular weight, narrow molecular weight distribution, and controlled composition to address as accurately as possible known molecular weight requirements. 8 In particular, influence of the macromolecular structure of the OEGMA copolymers (especially the influence of the OEG block) on their ability to condense pDNA and the physiochemical properties of the resulting gene vector particles were investigated in detail. In a second step, physiochemical properties were investigated in the context of the transfection efficiency of the gene vectors in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Tailor-Made Copolymers of Oligo(ethylene glycol) Methyl Ether Methacrylate and N,N-Dimethylaminoethyl Methacrylate as Nonviral Gene Transfer Agents: Influence of Macromolecular Structure on Gene Vector Particle Properties and Transfection Efficiency

et al. 2009

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Oligo(ethylene glycol) methyl ether methacrylates (OEGMA) of various chain lengths (i.e., 9, 23, or 45 EG units) and N,N-dimethylaminoethyl methacrylate (DMAEMA) were copolymerized by atom transfer radical polymerization (ATRP), yielding well-defined P(DMAEMA-co-OEGMA) copolymers with increasing OEGMA molar fractions (F OEGMA) but a comparable degree of polymerization (DP ∼ 120). Increase of both F OEGMA and OEGMA chain lengths correlated inversely with gene vector size, morphology, and zeta potential. P(DMAEMA-co-OEGMA) copolymers prevented gene vector aggregation at high plasmid DNA (pDNA) concentrations in isotonic solution and did not induce cytotoxicity even at high concentrations. Transfection efficiency of the most efficient P(DMAEMA-co-OEGMA) copolymers was found to be >10-fold lower compared with branched polyethylenimine (PEI) 25 kDa. Although OEGMA copolymerization largely reduced gene vector binding with the cell surface, cellular internalization of the bound complexes was less affected. These observations suggest that inefficient endolysosomal escape limits transfection efficiency of P(DMAEMA-co-OEGMA) copolymer gene vectors. Despite this observation, optimized p(DMAEMA-co-OEGMA) gene vectors remained stable under conditions for in vivo application leading to 7-fold greater gene expression in the lungs compared with PEI. Tailor-made P(DMAEMA-co-OEGMA) copolymers are promising nonviral gene transfer agents that fulfill the requirements for successful in vivo gene delivery.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Tailor-Made Copolymers of Oligo(ethylene glycol) Methyl Ether Methacrylate and N,N-Dimethylaminoethyl Methacrylate as Nonviral Gene Transfer Agents: Influence of Macromolecular Structure on Gene Vector Particle Properties and Transfection Efficiency

et al. 2009

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“…pDMAEMA was synthesized and characterized as described elsewhere (van de Wetering et al, 1997). The molecular mass of the DMAEMAmonomer was 157 g/mol.…”

Section: Cationic Polymersmentioning

confidence: 99%

Fluorescence Fluctuation Analysis for the Study of Interactions between Oligonucleotides and Polycationic Polymers

Rompaey¹,

Chen²,

Müller³

et al. 2001

Biological Chemistry

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“…8 The weight average molecular weight (M w ) and number average molecular weight ( M n ) of p( DMAEMA ) were determined by gel permeation chromatography. The used batch of p( DMAEMA ) had a M w of 2.1Â10 6 and a M n of 4.1Â10 4 .…”

Section: Polyplex Formation and Characterizationmentioning

confidence: 99%

“…18 After 30 minutes of maturation at room temperature, the formed polyplexes were analyzed for size distribution by dynamic light scattering and -potential as previously described. 8 The polyplexes had a mean diameter of approximately 80 nm with a -potential of + 25 ±30 mV ( in 5 mM HEPES, pH 7.4).…”

Section: Polyplex Formation and Characterizationmentioning

confidence: 99%

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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Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes

Cited by 241 publications

References 26 publications

Characterization of Tailor-Made Copolymers of Oligo(ethylene glycol) Methyl Ether Methacrylate and N,N-Dimethylaminoethyl Methacrylate as Nonviral Gene Transfer Agents: Influence of Macromolecular Structure on Gene Vector Particle Properties and Transfection Efficiency

Characterization of Tailor-Made Copolymers of Oligo(ethylene glycol) Methyl Ether Methacrylate and N,N-Dimethylaminoethyl Methacrylate as Nonviral Gene Transfer Agents: Influence of Macromolecular Structure on Gene Vector Particle Properties and Transfection Efficiency

Fluorescence Fluctuation Analysis for the Study of Interactions between Oligonucleotides and Polycationic Polymers

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

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