PDMAEMA Homopolymer Research Articles

Responsive Quaternized PDMAEMA Copolymers with Antimicrobial Action.

In this work, the antimicrobial action of partially quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMAEMA) copolymers using different alkyl halides is presented. The poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) homopolymer was synthesized by group transfer polymerization, followed by the modification of its tertiary amine groups, using bromoethane, iodoethane, bromohexane and bromoethanol, to introduce permanent cationic, quaternary ammonium salt moieties, randomly distributed along the polymer chains. In all cases, the degree of quaternization was low, at ~10 mol%, as verified by proton nuclear magnetic resonance spectroscopy to preserve the thermo-responsive character of the PDMAEMA precursor polymer. The biocidal activity of the lightly quaternized PQDMAEMA copolymers against Escherichia coli and Staphylococcus aureus was evaluated by calculating the minimum inhibitory concentration (MIC) as well as the minimum bactericidal concentration (MBC) of the polymers and by comparing them to the respective values of the precursor non-quaternized PDMAEMA homopolymer. The antibacterial mechanism of action in the solution was studied by zeta potential measurements, scanning electron microscopy and protein leakage tests signifying the disruption of the outer membrane of the bacterial cells to release their periplasmic proteins.

Swelling of multi-responsive spherical polyelectrolyte brushes across a wide range of grafting densities

Multi-stimulus responsive weak polyelectrolyte brushes were grafted by surface-initiated atom transfer radical polymerization from spherical silica nanoparticles across a wide range of grafting densities approaching the limit of close packing of grafting sites: a regime not previously explored in the brush swelling literature. Brushes consisted of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) homopolymers or poly(2-(dimethylamino)ethyl methacrylate)-r-poly(4-metharyloyloxyazobenzene) random copolymers P (DMAEMA-r-MOAB) and were subjected to pH-, temperature-, and photoisomerization-induced swelling and deswelling. Homopolymer brushes were prepared at grafting densities ranging from 0.12 to 1.4 nm−2 and number average degrees of polymerization ranging from 300 to 1200. Two copolymer brushes with 8 mol% and 13 mol% of the nonionizable, photoresponsive MOAB units were compared with homopolymer brushes prepared at similar grafting densities and degrees of polymerization. Dynamic light scattering was used to measure the hydrodynamic radius of grafted nanoparticles, and thus brush thickness, in water. Brush swelling in response to increased DMAEMA protonation followed a single scaling behavior across the full range of degrees of polymerization and grafting densities. Incorporating azobenzene-containing MOAB comonomers introduced a modest photoresponsive control of brush swelling and decreased the brush thickness relative to the comparable PDMAEMA homopolymer brush, without affecting the scaling with respect to protonation. PDMAEMA brushes exhibited a pH-dependent lower critical solution temperature behavior, resulting in a thermal collapse of up to 50% upon heating. This work demonstrates that scaling behaviors previously tested at low grafting densities hold for extremely high grafting densities and that they are unaffected by moderate nonionizable comonomer content.

Artificial chaperones based on thermoresponsive polymers recognize the unfolded state of the protein

Stabilization of the enzymes under stress conditions is of special interest for modern biochemistry, bioengineering, as well as for formulation and target delivery of protein-based drugs. Aiming to achieve an efficient stabilization at elevated temperature with no influence on the enzyme under normal conditions, we studied chaperone-like activity of thermoresponsive polymers based on poly(dimethylaminoethyl methacrylate) (PDMAEMA) toward two different proteins, glyceraldehyde-3-phosphate dehydrogenase and chicken egg lysozyme. The polymers has been shown to do not interact with the folded protein at room temperature but form a complex upon heating to either protein unfolding or polymer phase transition temperature. A PDMAEMA-PEO block copolymer with a dodecyl end-group (d-PDMAEMA-PEO) as well as PDMAEMA-PEO without the dodecyl groups protected the denatured protein against aggregation in contrast to PDMAEMA homopolymer. No effect of the polymers on the enzymatic activity of the client protein was observed at room temperature. The polymers also partially protected the enzyme against inactivation at high temperature. The results provide a platform for creation of artificial chaperones with unfolded protein recognition which is a major feature of natural chaperones.

Antibacterial poly{(4‐vinyl phenylboronic acid)‐co‐[2‐(dimethylamino)ethyl methacrylate]} copolymers and their application in water‐based paints

ABSTRACTHerein, we report the synthesis of poly(4‐vinylphenylboronic acid) (PVPBA) and poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) homopolymers, copolymers, and their methyl, pentyl, and octyl quaternized forms as dopant in water‐based permanent antibacterial paints. Both quaternized and nonquaternized forms of P(VPBA‐co‐DMAEMA) copolymers have reflected higher MIC values relative to PDMAEMA homopolymers. High molecular weight copolymers were more active against Escherichia coli ATCC 25922, contrarily, lower molecular weight copolymers showed higher antibacterial activity against Staphylococcus aureus ATCC 25923. The paint films prepared with quaternized PDMAEMA homopolymers with a weight of 10% showed better antibacterial activity in water and airborne tests than the copolymers. However, it has been shown that the inadequate anti‐biofilm properties of homopolymer‐containing paint films are overcome with the VPBA content of the copolymer structure and the most effective antibacterial and anti‐biofilm properties have been obtained with paint films containing P(VPBA‐co‐5QDMAEMA) copolymers. These paint films, which can maintain antibacterial and anti‐biofilm properties for at least 1 year, have the potential to be an alternative to Ag/Cl based solid surfaces which require the active substance to be regenerated. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46245.

Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(β-amino ester) Results in a Strong and Synergistic Transfection Activity.

This work reports an innovative and very effective gene delivery nanosystem, based on the combination of poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(β-amino ester) (PβAE) homopolymers, that has the capacity to efficiently deliver genetic material into target cells, even in the presence of serum. The best formulation, prepared with the combination PDMAEMA/4PβAE at the 25/1 nitrogen/phosphate (N/P) ratio, presented a 700-fold and 220-fold higher transfection activity than that obtained with branched polyethylenimine (PEI)-based polyplexes and block copolymer-based polyplexes, respectively. This new nanocarrier revealed high transgene expression in different human cells, including hard-to-transfect normal human astrocytes. The polyplexes presented high protection of genetic material and reduced sizes, which are suitable physicochemical properties for in vivo applications. Overall, this study demonstrates that the combination of PDMAEMA and PβAE homopolymers resulted in a noticeable and synergistic effect in terms of transfection activity, without causing substantial toxicity, constituting a new platform for the development of gene delivery nanosystems.

A facile route towards PDMAEMA homopolymer amphiphiles.

Well-defined poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) has been modified at low degrees of quaternization of the tertiary amine groups using alkyl halides with long alkyl chains as the quaternization agents. The resulting PDMAEMA-co-PQDMAEMA copolymers were studied in aqueous solution using potentiometric titrations, turbidimetry, surface tensiometry, dynamic light scattering and zeta potential measurements. An increase of the hydrophilicity of the precursor polymer, leading to an increase or even elimination of the lower critical solution temperature (LCST) for the quaternized copolymers was found; this extended the temperature range of the stable polymer solution. At the same time, it was shown that the hydrophobic character of the polymer increases upon quaternization, leading to higher surface activity compared to the precursor PDMAEMA homopolymer, and, thus, to more effective polymeric surfactants. This contradiction in the copolymer behavior was attributed to the interplay between the polymer self-assembly in the aqueous medium and the polymer adsorption at the air/water interface, which dominate the cloud point and the surface properties, respectively.

Nano-Sized Sunflower Polycations As Effective Gene Transfer Vehicles.

The architecture of polycations plays an important role in both gene transfection efficiency and cytotoxicity. In this work, a new polymer, sunflower poly(2-dimethyl amino)ethyl methacrylate) (pDMAEMA), is prepared by atom transfer radical polymerization and employed as nucleic acid carriers compared to linear pDMAEMA homopolymer and comb pDMAEMA. The sunflower pDMAEMAs show higher IC50 , greater buffering capacity, and stronger binding capacity toward plasmid DNA than their linear and comb counterparts. In vitro transfection studies demonstrate that sunflower pDMAEMAs exhibit high transfection efficiency as well as relatively low cytotoxicity in complete growth medium. In vivo gene delivery by intraventricular injection to the brain shows that sunflower polymer delivers plasmid DNA more effectively than comb polymer. This study provides a new insight into the relationship between polymeric architecture and gene delivery capability, and as well as a useful means to design potent vectors for successful gene delivery.

Water-Dispersible Silica-Polyelectrolyte Nanocomposites Prepared via Acid-Triggered Polycondensation of Silicic Acid and Directed by Polycations.

The present work describes the acid-triggered condensation of silicic acid, Si(OH)4, as directed by selected polycations in aqueous solution in the pH range of 6.5–8.0 at room temperature, without the use of additional solvents or surfactants. This process results in the formation of silica-polyelectrolyte (S-PE) nanocomposites in the form of precipitate or water-dispersible particles. The mean hydrodynamic diameter (dh) of size distributions of the prepared water-dispersible S-PE composites is presented as a function of the solution pH at which the composite formation was achieved. Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and block copolymers of DMAEMA and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) were used as weak polyelectrolytes in S-PE composite formation. The activity of the strong polyelectrolytes poly(methacryloxyethyl trimethylammonium iodide) (PMOTAI) and PMOTAI-b-POEGMA in S-PE formation is also examined. The effect of polyelectrolyte strength and the OEGMA block on the formation of the S-PE composites is assessed with respect to the S-PE composites prepared using the PDMAEMA homopolymer. In the presence of the PDMAEMA60 homopolymer (Mw = 9400 g/mol), the size of the dispersible S-PE composites increases with solution pH in the range pH 6.6–8.1, from dh = 30 nm to dh = 800 nm. S-PDMAEMA60 prepared at pH 7.8 contained 66% silica by mass (TGA). The increase in dispersible S-PE particle size is diminished when directed by PDMAEMA300 (Mw = 47,000 g/mol), reaching a maximum of dh = 75 nm. S-PE composites formed using PDMAEMA-b-POEGMA remain in the range dh = 20–30 nm across this same pH regime. Precipitated S-PE composites were obtained as spheres of up to 200 nm in diameter (SEM) and up to 65% mass content of silica (TGA). The conditions of pH for the preparation of dispersible and precipitate S-PE nanocomposites, as directed by the five selected polyelectrolytes PDMAEMA60, PDMAEMA300, PMOTAI60, PDMAEMA60-b-POEGMA38 and PMOTAI60-b-POEGMA38 is summarized.

Cationic Micelles Based on Polyhedral Oligomeric Silsesquioxanes for Enhanced Gene Transfection

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers, poly(2-(dimethylamino)ethyl methacrylate)-poly (methacrylate isobutyl polyhedral oligomeric silsesquioxane) (PDMAEMA-POSS) copolymers are reported. The hydrophobic POSS interior allows a cell-sensitizing drug such as paclitaxel to be incorporated, whereas the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency compared with polyethylenimine or PDMAEMA homopolymers.

PH- and Ionic-Strength-Induced Contraction of Polybasic Micelles in Buffered Aqueous Solutions

We report the synthesis and characterization of poly(dimethylaminoethyl methacrylate)-block-poly(styrene) (PDMAEMA-b-PS) diblock copolymers by RAFT polymerization. These polymers form uniform spherical micelles with dispersities less than 0.05 upon addition of aqueous buffer to polymer solutions in DMF. Potentiometric titrations under constant ionic strength conditions yield the first rigorous ionic-strength-effective pKa correspondence for PDMAEMA homopolymers and micelles. We demonstrate that the effective polymer pKa increases monotonically toward the monomer pKa with increasing ionic strength, but decreases slightly upon association of polymer chains into micelles. We further characterize the pH- and ionic-strength-induced contraction of the micelle coronas in buffered aqueous solutions. In monoprotic buffers, the micelle corona behaves as a salted osmotic brush, as has been observed for other block polyelectrolyte micelle systems in unbuffered solutions. In polyprotic buffers, however, we observe an ...

Synthesis of pH- and thermo-responsive poly (ε-caprolactone-b-4-vinyl benzyl-g-dimethyl amino ethyl methacrylate) brush type graft copolymers via RAFT polymerization

A novel pH- and thermo-responsive poly (e-caprolactone-b-4-vinyl benzyl-g-2-(dimethyl amino ethyl) methacrylate), poly (CL-b-VB-g-DMAEMA), brush type copolymer has been described. In this study, a reversible addition–fragmentation chain transfer (RAFT) agent, 1,2-propanediol-3-ethyl xanthogenate, was obtained through the reaction of 3-chloro-1,2-propanediol with potassium salt of ethyl xanthogenate. Poly (CL-b-VB) block copolymer was synthesized in one-pot polymerization of e-caprolactone (CL) and 4-vinyl benzyl chloride (VB) using a new dual macro-RAFT agent. In the second step of the work, chloride side groups of poly-VB in poly (CL-b-VB) block copolymer were reacted with potassium salt of ethyl xanthogenate to obtain another novel macro-RAFT agent, poly (CL-b-VB)-g-xanthate (PCL-PVB-Xa). Controlled free radical living polymerization of 2-(dimethylaminoethyl) methacrylate (DMAEMA) was initiated with this PCL-VB-Xa macro-RAFT agent to obtain new poly (CL-b-VB-g-DMAEMA) comb type pH- and thermo-responsive heterograft copolymer. The homopolymer was soluble in water at pH = 10–11 and not soluble at pH = 12.5. A pH-sensitive feature of the brush type graft copolymer was observed between pH 9.4 and 11.5 in view of their swelling/solution properties depending on the acrylic polymer inclusion. The LCST values of the multiblock brush type copolymers were found to be as low as 42.8 °C, while that of PDMAEMA homopolymer was 46.6 °C. The characterization of the products was achieved using gel-permeation chromatography (GPC), thermal, and spectrometric analysis techniques. pH- and thermo-responsiveness of the copolymers were verified by surface tension and zeta potential measurements.

Nucleic acid delivery systems based on poly(galactosyl ureaethyl methacrylate-b-dimethylamino ethyl methacrylate) diblock copolymers

Elevated low-density-lipoprotein cholesterol (LDL-C) level is a major risk factor leading to cardiovascular diseases. Therefore, since the proprotein convertase subtilisin kexin type 9 (PCSK9) regulates LDL-C receptors, it represents the appropriate target for cholesterol-lowering gene therapy. However, although delivery of antisense oligonucleotides (ODNs) is a promising therapeutic method for the treatment of several diseases, it is fundamental to develop new and efficacious carriers that transport the ODNs into the target cell in a nontoxic manner.This study reports on the synthesis, characterization and in vitro testing of a new liver specific carrier based on linear cationic diblock glycopolymer composed of galactosyl ureaethyl methacrylate (GAMA) and the primary amine-containing dimethylamino ethyl methacrylate (DMAEMA). Delivery experiments proved that the poly(galactosyl ureaethyl methacrylate -b-dimethylamino ethyl methacrylate) diblock copolymer (pGa4D47), internalized in a receptor-mediated manner, exhibited a much faster nuclear transportation than ODNs carried by pDMAEMA homopolymer or glycopolymer bearing glucose moieties.

Breaking of the Bancroft rule for multiple emulsions stabilized by a single stimulable polymer.

We investigated emulsions of water and toluene stabilized by (co)polymers consisting of styrene (S) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomer units with different compositions and structures such as a PDMAEMA homopolymer, a P(S-co-DMAEMA) random copolymer and various PS-b-PDMAEMA and PS-b-(S-co-DMAEMA) block copolymers. The model system is used to study the fundamental conditions under which the different kinds of polymer-stabilized emulsions (direct oil in water, inverse water in oil and multiple emulsions) are stabilized or destabilized by pH change (at constant temperature). Polymer properties like chain conformation at the toluene-water interface as probed by SANS and neutron reflectivity at the liquid-liquid interface, the oil-water partitioning of the polymer chains (Bancroft's rule of thumb) as determined by UV spectroscopy and interfacial tensions measured by the rising and spinning drop techniques are determined. Overall, results evidence that the curvature sign, as defined by positive and negative values as the chain segments occupy preferentially the water and toluene sides of the interface respectively, reliably predicts the emulsion kind. In contrast, the Bancroft rule failed at foreseeing the emulsion type. In the region of near zero curvature the crossover from direct to inverse emulsions occurs through the formation of either unstable coexisting direct and inverse emulsions (i) or multiple emulsions (ii). The high compact adsorption of the chains at the interface as shown by low interfacial tension values does not allow to discriminate between both cases. However, the toluene-water partitioning of the polymeric emulsifier is still a key factor driving the formation of (i) or (ii) emulsions. Interestingly, the stabilization of the multiple emulsions can be tuned to a large extent as the toluene-water polymer partitioning can be adjusted using quite a large number of physico-chemical parameters linked to polymer architecture like diblock length ratio or polymer total molar mass, for example. Moreover, we show that monitoring the oil-water partitioning aspect of the emulsion system can also be used to lower the interfacial tension at low pH to values slightly higher than 0.01 mN m(-1), irrespective of the curvature sign.

Co-delivery of drug and DNA from cationic dual-responsive micelles derived from poly(DMAEMA-co-PPGMA)

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers with poly(dimethylaminoethyl methacrylate) (PDMAEMA), and poly(propylene glycol methacrylate) (PPGMA) segments is reported. The hydrophobic PPGMA interior allows a cell-sensitizing drug such as paclitaxel to be incorporated while the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency as compared to PEI or PDMAEMA homopolymers.

Incorporation of Poly[(R)‐3‐hydroxybutyrate] into Cationic Copolymers Based on Poly(2‐(dimethylamino)ethyl methacrylate) to Improve Gene Delivery

The synthesis and gene transfection efficiency of a series of novel amphiphilic triblock copolymers with two hydrophilic poly(2-(dimethylamino)ethyl methacrylate) (DMAEMA) blocks flanking a central hydrophobic poly[(R)-3-hydroxybutyrate] (PHB) block is reported. These copolymers have significantly lower toxicity compared to the polyethyleneimine (PEI) and PDMAEMA homopolymer. Unexpectedly, the incorporation of PHB significantly improves the gene transfection efficiency as compared to PEI or PDMAEMA homopolymers.

Effect of Composition of PDMAEMA-b-PAA Block Copolymers on Their pH- and Temperature-Responsive Behaviors

A series of poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) homopolymers and poly(2-(dimethylamino)ethyl methacrylate)-b-poly(acrylic acid) (PDMAEMA-b-PAA) diblock copolymers were synthesized by atomic transfer radical polymerization. Thanks to a fine-tuning of the hydrophobic-hydrophilic balance by varying the molecular weight of the polymers and the pH of the aqueous solutions, as well as the composition for the block copolymers, the lower critical solution temperature (LCST) and the aggregation-dissolution kinetics of PDMAEMA homopolymers and PDMAEMA-b-PAA block copolymers can be adjusted. For the block copolymers, the results show that larger relative size of the PDMAEMA blocks leads to an increasing tendency to form micellar aggregates and a decrease of the LCST of the aqueous solution, which is consistent with the increasing copolymer hydrophobicity. A significant difference of the stimuli-responsive behavior between PDMAEMA-rich and PAA-rich copolymers is observed, because the former exhibit thermo-responsive behavior in a broad temperature range of 40-60 °C in basic media, while the pH-responsive behavior is dominant, and only a weak thermo-responsive behavior is exhibited around the specific isoelectric point (IEP) in the latter case. The aggregation rate is strongly influenced by temperature, molecular weight, structure, and composition of the polymer. Specifically, temperature has a stronger effect than the molar ratio of the PDMAEMA segment in the copolymer (related to its hydrophobicity) and the chain molecular weight, although the PDMAEMA-b-PAA copolymers show faster aggregation rate than do the PDMAEMA homopolymers.

Dual responsive micelles based on poly[(R)-3-hydroxybutyrate] and poly(2-(di-methylamino)ethyl methacrylate) for effective doxorubicin delivery

We present novel pH and thermo-sensitive amphiphilic triblock copolymers with two hydrophilic poly(2-(di-methylamino)ethyl methacrylate) (DMAEMA) blocks flanking a central hydrophobic poly[(R)-3-hydroxybutyrate] block. The release of doxorubicin from the micelles can be controlled by pH and temperature triggers. Using this system, extremely long duration sustained drug release was achieved, better than most micelle systems currently described in the literature. Sustained release of the drug was achieved at pH 7 and 37 °C. Cytotoxicity tests of the copolymers showed that they have significantly lower toxicity towards fibroblast cells compared with the PDMAEMA homopolymer. The doxorubicin-loaded micelles were effective in controlling the growth of HeLa cells. The results demonstrated that the copolymers could be potentially used in chemotherapeutic applications.

Stable gene transfection mediated by polysulfobetaine/PDMAEMA diblock copolymer in salted medium

Cationic polyplexes would aggregate immediately after intravenous injection due to the plasma proteins and high ionic strength. A cationic polyplexes with long-term and salt stability was very important for a systemic gene therapy. In this research, a polysulfobetaine-b-polycation diblock copolymer composed of cationic block of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and zwtterionic block of poly(propylsulfonate dimethylammonium ethylmethacrylate) (PSPE) was conveniently synthesized by atom transfer radical polymerization method to obtain a cationic polymers with long-term and salt stability. The results of agarose gel electrophoresis and transmission electron microscope indicated that copolymerization of PSPE did not compromise the DNA condensation ability of PDMAEMA, meanwhile exhibiting lower cytotoxicity. The effect of salt on the absorbance and particle size of PDMAEMA100/DNA and PDMAEMA100-PSPEy/DNA complexes was investigated, which showed that PSPE block could increase the resistance of polyplexes against salt-induced aggregation owing to the antielectrolyte effect. In comparison with PDMAEMA homopolymer, PDMAEMA100-PSPEy retained more stable gene transfection in a certain range of salt concentration. The expression of red fluorescence protein (RFP) was evaluated by small animal in vivo fluorescence imaging system and the results showed that the expression of RFP was much higher in the mice injected with PDMAEMA100-PSPE20/pDNA-RFP than with PDMAEMA/pDNA-RFP. Both in vitro and in vivo results suggested that PDMAEMA-PSPE diblock copolymer may be potentially used as a vector for systemic gene therapy.

Poly(2-dimethylamino ethylmethacrylate)-Based Polymers To Camouflage Red Blood Cell Antigens

Poly(2-dimethylamino-ethylmethacrylate) (PDMAEMA) is a cationic polymer when dissolved in a 7.4 pH fluid. Owing to its ionic nature, this polycation interacts with the negatively charged cell membrane surface of red blood cells (RBCs). The electrostatic self-assembly of PDMAEMA on RBCs membrane can be employed for inducing the formation of a polymeric shield camouflaging blood group antigens on RBCs as a valuable strategy for developing "universal RBCs" for blood transfusion. The purpose of this research was to evaluate the camouflaging ability of PDMAEMA homopolymers and PDMAEMA-co-poly(ethylene glycol) copolymers differing in molecular weight and architecture. Surprisingly, the PDMAEMAs caused a partially masking, no masking, and sensitization of the same RBCs population. The MW and architecture of the polymers as well as temperature of PDMAEMA-RBCs treatment influenced the results observed. Herein, the very particular reactivity of PDMAEMAs and RBCs is analyzed and discussed.

Reversibly Shielded DNA Polyplexes Based on Bioreducible PDMAEMA-SS-PEG-SS-PDMAEMA Triblock Copolymers Mediate Markedly Enhanced Nonviral Gene Transfection

Reversibly shielded DNA polyplexes based on bioreducible poly(dimethylaminoethyl methacrylate)-SS-poly(ethylene glycol)-SS-poly(dimethylaminoethyl methacrylate) (PDMAEMA-SS-PEG-SS-PDMAEMA) triblock copolymers were designed, prepared and investigated for in vitro gene transfection. Two PDMAEMA-SS-PEG-SS-PDMAEMA copolymers with controlled compositions, 6.6-6-6.6 and 13-6-13 kDa, were obtained by reversible addition-fragmentation chain transfer (RAFT) polymerization of dimethylaminoethyl methacrylate (DMAEMA) using CPADN-SS-PEG-SS-CPADN (CPADN: 4-cyanopentanoic acid dithionaphthalenoate; PEG: 6 kDa) as a macro-RAFT agent. Like their nonreducible PDMAEMA-PEG-PDMAEMA analogues, PDMAEMA-SS-PEG-SS-PDMAEMA triblock copolymers could effectively condense DNA into small particles with average diameters less than 120 nm and close to neutral zeta potentials (0 ∼ +6 mV) at and above an N/P ratio of 3/1. The resulting polyplexes showed excellent colloidal stability against 150 mM NaCl, which contrasts with polyplexes of 20 kDa PDMAEMA homopolymer. In the presence of 10 mM dithiothreitol (DTT), however, polyplexes of PDMAEMA-SS-PEG-SS-PDMAEMA were rapidly deshielded and unpacked, as revealed by significant increase of positive surface charges as well as increase of particle sizes to over 1000 nm. Release of DNA in response to 10 mM DTT was further confirmed by gel retardation assays. These polyplexes, either stably or reversibly shielded, revealed a low cytotoxicity (over 80% cell viability) at and below an N/P ratio of 12/1. Notably, in vitro transfection studies showed that reversibly shielded polyplexes afforded up to 28 times higher transfection efficacy as compared to stably shielded control under otherwise the same conditions. Confocal laser scanning microscope (CLSM) studies revealed that reversibly shielded polyplexes efficiently delivered and released pDNA into the perinuclei region as well as nuclei of COS-7 cells. Hence, reduction-sensitive reversibly shielded DNA polyplexes based on PDMAEMA-SS-PEG-SS-PDMAEMA are highly promising for nonviral gene transfection.