Enzymatic PEGylated Poly(lactone-co-β-amino ester) Nanoparticles as Biodegradable, Biocompatible and Stable Vectors for Gene Delivery

Dec 18, 2015ACS applied materials & interfaces

Enzyme-made biodegradable and stable coated nanoparticles for safe gene delivery

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Abstract

The PEG-PPM-15% PDL micelle particles exhibited high DNA-binding ability and the fastest cellular uptake rate.

New gene delivery systems were developed using biodegradable, stable, and low-toxicity PEGylated block copolymers.
Polyplex micelle nanoparticles formed by these copolymers have desirable sizes ranging from 70 to 140 nm.
These micelles are stable in serum protein-containing environments and have low critical micelle concentrations.
The presence of tertiary amine groups in the copolymer chains may facilitate effective escape from endosomal degradation.
In vitro assays indicate that the copolymers are nonhemolytic and exhibit minimal toxicity to COS-7 cells at concentrations up to 200 μg/mL.

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We have developed new, efficient gene delivery systems based on PEGylated poly(lactone-co-β-amino ester) block copolymers that are biodegradable, stable and low in toxicity. The PEG-poly[PDL-co-3-(4-(methylene)piperidin-1-yl)propanoate] (PEG-PPM) diblock and PPM-PEG-PPM triblock copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL) and ethyl 3-(4-(hydroxymethyl)piperidin-1-yl)propanoate (EHMPP) with an appropriate PEG (MeO-PEG-OH or HO-PEG-OH). The amphiphilic block copolymers are capable of condensing DNA in aqueous medium via a self-assembly process to form polyplex micelle nanoparticles with desirable particle sizes (70-140 nm). These micelles possess low CMC values and are stable in the medium containing serum protein molecules (FBS). Among the PEG-PPM and PPM-PEG-PPM micelles, the PEG-PPM-15% PDL micelle particles exhibited high DNA-binding ability, the fastest cellular uptake rate and highest gene transfection efficacy. Flow cytometry analysis shows that LucDNA/PEG-PPM-15% PDL polyplex micelles can effectively escape from endosomal degradation after cellular uptake likely due to the presence of the tertiary amine groups in the copolymer chains that act as proton sponges. In vitro cytotoxicity and hemolysis assay experiments indicate that all copolymer samples are nonhemolytic and have minimal toxicity toward COS-7 cells within the polymer concentration range (≤200 μg/mL) used for the gene transfection. These results demonstrate that the PEGylated poly(lactone-co-β-amino ester) block copolymers are promising new vectors for gene delivery applications.

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Enzymatic PEGylated Poly(lactone-co-β-amino ester) Nanoparticles as Biodegradable, Biocompatible and Stable Vectors for Gene Delivery

Abstract

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