Novel Cationic Triblock Copolymer of Poly[2-(dimethylamino)ethyl methacrylate]-block-poly(β-amino ester)-block-poly[2-(dimethylamino)ethyl methacrylate]: A Promising Non-Viral Gene Delivery System

Abstract

This manuscript reports the synthesis of a new cationic block copolymer based on poly[2-(dimethylamino)ethyl methacrylate] and poly(β-amino ester) from different polymerization strategies. For the first time, it is proposed a triblock copolymer based only on cationic segments, aiming a high biocompatibility, enhanced buffering capacity and stimuli-responsive character in a single structure. The new block copolymer successfully condensed the plasmid DNA into nanosized polyplexes. The polyplexes were tested in two different cell lines revealing ∼4-fold and ∼6-fold (in HeLa cells), and ∼11-fold (in COS-7 cells) higher transgene expression than branched PEI and TurboFect™, respectively. These results show that this new block copolymer is a promising candidate to be used as a polymeric non-viral vector.

Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-Based Polyplexes as Serum-Tolerant Nanosystems for Enhanced Gene Delivery

“…26 Consequently, the length of the PAMA chains is shown to have a crucial role in transfection activity. This relationship between the molecular weight of the cationic polymers and the polyplex transfection capacity has been reported for other polymers, such as PEI, 27 PDMAEMA, 28 chitosan, 29 and PβAE. 10 When transfection was performed in a serum-free medium (Figure 1a), in general, the biological activity of the generated polyplexes decreased as a function of N/P ratio, the maximum transgene expression being obtained at the 10:1 N/P ratio.…”

Amphiphilic Graft Copolymers Capable of Mixed-Mode Interaction as Alternative Nonviral Transfection Agents

“…The ATRP initiator 2-(2-azidoethoxy) ethyl bromoisobutyrate (N 3 E i BBr) was prepared following procedures previously reported. 35,37 Briefly, PPxMy (0.5 g, 0.054 mmol, mean number of alkyne groups = 5), N 3 E i BBr (92 mg, 0.329 mmol), and Bpy (34 mg, 0.218 mmol) were dissolved in dry THF (11 mL) and degassed with argon for 20 min. The ATRP initiator was then bound to mPEG-b-P(CL-co-MPC) via a click-reaction to form a macroinitiator (mPEG-b-P(CL-co-(MPC-Br)).…”

“…The mPEG- b -P­(CL- co -(MPC- g -PDMAEMA)) (PP x D y ) grafted structures were produced by a combination of CuAAC and ATRP, using the same catalytic complex for both reactions, namely, CuBr/2,2′-bipyridyl (Bpy). The ATRP initiator 2-(2-azidoethoxy) ethyl bromoisobutyrate (N 3 E i BBr) was prepared following procedures previously reported. , Briefly, PP x M y (0.5 g, 0.054 mmol, mean number of alkyne groups = 5), N 3 E i BBr (92 mg, 0.329 mmol), and Bpy (34 mg, 0.218 mmol) were dissolved in dry THF (11 mL) and degassed with argon for 20 min. The ATRP initiator was then bound to mPEG- b -P­(CL- co -MPC) via a click-reaction to form a macroinitiator (mPEG- b -P­(CL- co -(MPC-Br)).…”

The Promising Nanocarrier for Doxorubicin and siRNA Co-delivery by PDMAEMA-based Amphiphilic Nanomicelles

“…Among the various nonviral vectors, cationic polymers are attractive and effective for siRNA delivery in vitro and in vivo, such as polyethylenimine (PEI), , chitosan, 2-guanidinoethyl methacrylate (GEMA), poly­( l -lysine) (PLL), polyamidoamine (PAMAM), and 2-(dimethylamino) ethyl methacrylate (DMAEMA) . Among them, DMAEMA has been considered as excellent DNA/siRNA carriers due to its low cytotoxicity and buffering capatity (known as proton sponge effect) for endosomal escape . Besides, poly­(2-(dimethylamino)­ethyl methacrylate) (PDMAEMA) exhibits other advantages: copolymer could be easily synthesized by atom transfer radical polymerization (ATRP) or reversible addition–fragmentation transfer (RAFT), molecular weights are controlled, and different architectures (such as block and graft) could be fabricated .…”

“…34 Among them, DMAEMA has been considered as excellent DNA/siRNA carriers due to its low cytotoxicity and buffering capatity (known as proton sponge effect) for endosomal escape. 35 Besides, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) exhibits other advantages: copolymer could be easily synthesized by atom transfer radical polymerization (ATRP) or reversible addition−fragmentation transfer (RAFT), molecular weights are controlled, and different architectures (such as block and graft) could be fabricated. 36 In our previous work, a series of PDMAEMAbased amphiphilic cationic polymers have been developed and evaluated on DNA/siRNA delivery.…”