Natural steroid-based cationic copolymers cholesterol/diosgenin- r -PDMAEMAs and their pDNA nanoplexes: impact of steroid structures and hydrophobic/hydrophilic ratios on pDNA delivery.

Using natural-based lipids to construct biocompatible, controllable and efficient nanocarriers and elucidating their structure-function relationships, was regarded as an important area for creating sustainable biomaterials. Herein, we utilized two natural steroids: cholesterol and diosgenin (bearing different hydrophobic tails) as the building blocks, to synthesize a series of natural steroid-based cationic random copolymers PMA6Chol- r -PDMAEMA and PMA6Dios- r -PDMAEMA via RAFT polymerization. The results demonstrated that the steroid- r -PDMAEMA copolymers could efficiently bind pDNA (N/P < 3.0) and then form near-spherical shape (142-449 nm) and positively-charged (+11.5 to +19.6 mV) nanoparticles. The in vitro cytotoxicity and gene transfection efficiency greatly depend on the steroid hydrophobic tail structures and steroid/PDMAEMA block ratios. Optimum transfection efficiency of the (Chol-P1/pDNA and Dios-P3/pDNA) nanoplexes could reach to 18.1-31.2% of the PEI-25K/pDNA complex. Moreover, all of the steroid- r -PDMAEMA/Cy3-pDNA nanoplexes have an obvious "lysosome localization" effect, indicating the steroid structures do not remarkably influence the intracellular localization behaviors of these nanoplexes.