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

Zhao Wang; Jingjing Sun; Mingrui Li; Ting Luo; Yulin Shen; Amin Cao; Ruilong Sheng

doi:10.1039/d1ra00223f

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

RSC Adv. 2021 Jun 1;11(32):19450-19460. doi: 10.1039/d1ra00223f. eCollection 2021 May 27.

Authors

Zhao Wang^{1

2

3}, Jingjing Sun^{1

3}, Mingrui Li³, Ting Luo³, Yulin Shen², Amin Cao³, Ruilong Sheng^{1

3

4}

Affiliations

¹ Department of Radiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072 China.
² School of Material Engineering, Jinling Institute of Technology Nanjing 211169 China.
³ CAS Key Laboratory of Synthetic and Self-assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences 345 Lingling Road Shanghai 200032 China.
⁴ CQM-Centro de Quimica da Madeira, Universidade da Madeira Campus da Penteada Funchal Madeira 9000-390 Portugal ruilong.sheng@staff.uma.pt.

Abstract

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.