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Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-based polyplexes as serum-tolerant nanosystems for enhanced gene delivery.

08:00 EDT 15th April 2019 | BioPortfolio

Summary of "Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-based polyplexes as serum-tolerant nanosystems for enhanced gene delivery."

PEGylation of cationic polyplexes has been used as a promising approach to enhance their stability and reduce unwanted interactions with biomolecules. However, this strategy generally has a negative effect on cellular uptake and, consequently, on transfection of target cells. In this work, we explore the impact of PEGylation on biological and physicochemical properties of poly(2-aminoethyl methacrylate) (PAMA)-based polyplexes. For this purpose, different tailor-made PEG-b-PAMA block copolymers, and the respective homopolymers, were synthesized using the controlled/"living" radical polymerization method based on activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The obtained data show that PEG-b-PAMA-based polyplexes exhibited much better transfection activity/cytotoxicity relationship than the corresponding non-PEGylated nanocarriers. The best formulation, prepared with the largest block copolymer (PEG45-b-PAMA168) at the 25/1 N/P ratio, presented a 350-fold higher transfection activity in the presence of serum than that obtained with polyplexes generated with gold standard bPEI. This higher transfection activity was associated to an improved capability to overcome the intracellular barriers, namely the release from the endolysosomal pathway and the vector unpacking and consequent DNA release from nanocarrier inside cells. Moreover, these nanosystems present suitable physicochemical properties for gene delivery namely reduced sizes, high DNA protection and colloidal stability. Overall, these findings demonstrate the high potential of the PEG45-b-PAMA168 block copolymer as gene delivery system.

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This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392
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A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.

A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins.

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A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.

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