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Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors.

ABSTRACT: The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s were measured by GPC. Agarose gel retardation assays showed that these materials have good DNA-binding ability and can retard the electrophoretic mobility of plasmid DNA (pDNA) at a weight ratio of 1. The formed polyplexes have proper sizes of around 200 nm and zeta-potential values of about 30-40 mV for cellular uptake. In vitro experiments revealed that polymer P2 gave higher transfection efficiency than PEI 25KDa and Lipofectamine 2000 with less toxicity, especially in 293 cells. Results demonstrate that such a type of degradable poly(amino ester) may serve as a promising non-viral gene vector.

SUBMITTER: Liu Q

PROVIDER: S-EPMC6154102 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors.

Liu Qiang Q Su Rong-Chuan RC Yi Wen-Jing WJ Zhao Zhi-Gang ZG

Molecules (Basel, Switzerland) 20170331 4

The development of gene delivery vectors with high efficiency and biocompatibility is one of the critical points of gene therapy. Two biodegradable poly(amino ester)s were synthesized via ring-opening polymerization between low molecular weight (LMW) PEI and diepoxide. The molecular weights of poly(amino ester)s were measured by GPC. Agarose gel retardation assays showed that these materials have good DNA-binding ability and can retard the electrophoretic mobility of plasmid DNA (pDNA) at a weig ...[more]

PMID: 28362336

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Project description:Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses. Upon introduction into a reducing environment, these disulfide-containing hydrogels cleave to present bound-thiol groups, yet remain in the bulk form at up to 66 mol% cystamine of the total amines. By controlling the molar fraction of cystamine, it was apparent that the thiol content varied human umbilical vein endothelial cell (HUVEC) viability IC50 values across an order of magnitude. Further, upon introduction of an enzymatic oxidative stress generator to the cell culture (HX/XO), pre-incubated thiolated hydrogel degradation products conferred cellular and mitochondrial protection from acute oxidative stress, whereas non-reduced disulfide-containing degradation products offered no protection. This polymer may be an advantageous implantable drug delivery system for use in acute oxidative stress prophylaxis and/or chronic oxidative stress cell therapies due to its solid/liquid reversibility in a redox environment, controlled thiolation, high loading capacity through covalent drug-addition, and simple post-synthesis modification which bound-thiols introduce. STATEMENT OF SIGNIFICANCE:In this work, we demonstrate a unique property of disulfide containing degradable biomaterials. By changing the redox state of the degradation products (from oxidized to reduced), it is possible to increase the IC50 of the material by an order of magnitude. This dramatic shift is linked directly to the oxidative stress response of the cells and suggests a possible mechanism by which one can tune the cellular response to degradable biomaterials.

Dataset Information

Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors.

Publications

Biodegradable Poly(Amino Ester) with Aromatic Backbone as Efficient Nonviral Gene Delivery Vectors.

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