Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes

Abstract

Viral-mediated gene delivery has been explored for the treatment and protection of cardiomyocytes, but so far there is only one report using cationic polymer for gene delivery to cardiomyocytes in spite of many advantages of polymer-mediated gene delivery. In this study, a cationic poly(b-amino ester) (PDMA) with a degradable backbone and cleavable side chains was synthesized by Michael addition reaction. The toxicity of PDMA to neonatal mouse cardiomyocytes (NMCMs) was significantly lower than that of polyethyleneimine (PEI). PDMA formed stable polyplexes with pEGFP. The dissociation of the polyplexes could be triggered by PDMA degradation, and the dissociation time was tunable via the polymer/pEGFP ratio. In vitro transfection showed that PDMA was an effective and low toxic gene delivery carrier for NMCMs. The PDMA/pEGFP polyplexes transfected EGFP gene to NMCMs with about 28% efficiency and caused little death. In contrast, a significant portion of cardiomyocytes cultured with PEI/pEGFP died.

Degradable Cisplatin-Releasing Core-Shell Nanogels from Zwitterionic Poly(β -Aminoester)-Graft-PEG for Cancer Chemotherapy

“…They have low toxicity and have been used for gene delivery because they generally carry cationic charges in water (Akinc et al 2003;Anderson, Lynn, and Langer 2003;Little et al 2004Little et al , 2005Shenoy et al 2005). We found that the polymerization of 2,2-bis(acryloxymethyl)propionic acid with amine monomers produced carboxylic acid-functionalized zwitterionic polymers (Xu et al 2006a). The polymer is water soluble and degradable.…”

“…The graft polymers were synthesized by cocondensation polymerization of 2,2-bis(acryloxymethyl)propionic acid and PEG with terminal 2,2-bis(acryloxymethyl)propionate with piperazine (Xu et al 2006a). The same type of diacrylates was used to make the PEG chains randomly distributed along the polymer backbones.…”

Nanoparticles as Nonviral Gene Delivery Vectors

“…Very recently, Liu and Reineke used poly (glycoamidoamine)s as carriers for gene delivery to cardiomyoblast cells [80], while Xu et al evaluated the transfection ability of a new poly ( -aminoester) derivative with pEGFP on neonatal mouse cardiomyocytes [81].…”

Nanopharmacology in translational hematology and oncology

“…[86][87][88] The main disadvantage is that PEG is not cell-specific, and one would need very high doses in order to achieve the desired concentration, leading to potentially serious side effects. 89,90 Thus, the need to improve current knowledge in the field and to produce other ligand molecules for aptamers functionalization. Aptamers are short, single-stranded oligonucleotides formed by 30-50 bases and they express minimal or even no antigenicity and immunogenicity, making them more suitable for in vivo use in clinical hematology and oncology.…”