Different types of degradable vectors from low-molecular-weight polycation-functionalized poly(aspartic acid) for efficient gene delivery.

Poly(aspartic acid) (PAsp) has been employed as the potential backbone for the preparation of efficient gene carriers, due to its low cytotoxicity, good biodegradability and excellent biocompatibility. In this work, the degradable linear or star-shaped PBLA was first prepared via ring-opining polymerization of ß-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized cyclodextrin cores. Then, PBLA was functionalized via aminolysis reaction with low-molecular-weight poly(2-(dimethylamino)ethyl methacrylate) with one terminal primary amine group (PDMAEMA-NH2), followed by addition of excess ED or ethanolamine (EA) to complete the aminolysis process. The obtained different types of cationic PAsp-based vectors including linear or star PAsp-PDM-NH2 and PAsp-PDM-OH exhibited good condensation capability and degradability, benefiting gene delivery process. In comparison with gold standard polyethylenimine (PEI, ∼ 25 kDa), the cationic PAsp-based vectors, particularly star-shaped ones, exhibited much better transfection performances.

Aminated poly(glycidyl methacrylate)s for constructing efficient gene carriers.

Aminated poly(glycidyl methacrylate) (PGMA) vectors could efficiently mediate gene delivery. Recently, we reported that ethanolamine (EA)-functionalized PGMA could provide high transfection efficiency, while exhibiting very low toxicity. Herein, different amine species, including 1-amino-2-propanol (AP1), 3-amino-2-propanol (AP2), EA, and N,N,-dimethylethylenediamine (DED), and its quaternized DED, were proposed to aminate PGMA. The DNA condensation abilities, pH buffering capacities, cytotoxicities, and gene transfection efficiencies of the resultant aminated PGMA vectors were systematically compared. Compared with EA, AP1 (or AP2) contains an additional methyl (or methylene) group. EA-, AP1-, and AP2-functionalized PGMA vectors exhibited similar condensation abilities. The methyl (from AP1) and methylene (from AP2) species could benefit the gene delivery. The transfection performance mediated by AP1-functionalized PGMA is best. DED possesses a tertiary amine group, which could be quaternized to further enhance the DNA condensation ability of aminated PGMA. No obvious increase in cytotoxicity of quaternized DED-aminated PGMA was observed. But both DED- and its quaternized counterpart-functionalized PGMA vectors exhibited very low pH buffering capacities, making them exhibit poor gene transfection performances. The current study would provide useful information for constructing better PGMA-based delivery systems with good biophysical properties.