Ghodke Sharwari B, Parkar Junaid N, Deshpande Aparna R, Dandekar Prajakta P, Jain Ratnesh D
Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019, India.
Department of Polymer & Surface Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019, India.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7500-7514. doi: 10.1021/acsabm.0c00717. Epub 2020 Oct 21.
A series of linear polyester-based, α-cyclodextrin (CD)-threaded polyrotaxanes (PRTx) were synthesized for siRNA delivery. The investigation into the effect of the presence of polyester linkages in polyrotaxane established the structural-activity relationship between polyrotaxane and siRNA transfection efficiency. The ester-based polyrotaxane exhibited higher threading efficiency than poly(ethylene glycol)-based polyrotaxane. The threading efficiency is the driving force for transfection, as it regulates the positive charge density on polyrotaxane. Polyester-based polyrotaxane formed stable and effective transfection nanoplexes with siRNA at lower N/P ratios, signifying the high gene loading capacity of the developed supramolecular vectors. Our findings suggest that biochemical properties of the transfection complexes depend on the structure of the axis and threading efficiency of polyrotaxane, which further influences the transfection efficiency. The enhanced gene silencing efficiency and safety are compared with those of extensively explored poly(ethylene glycol)-based polyrotaxane, polyethyleneimine (a gold standard), and lipofectamine (a commercial standard), which are used as siRNA delivery vectors.
合成了一系列基于线性聚酯的α-环糊精（CD）穿线聚轮烷（PRTx）用于小干扰RNA（siRNA）递送。对聚轮烷中聚酯键存在的影响进行的研究确立了聚轮烷与siRNA转染效率之间的构效关系。酯基聚轮烷比聚乙二醇基聚轮烷表现出更高的穿线效率。穿线效率是转染的驱动力，因为它调节聚轮烷上的正电荷密度。基于聚酯的聚轮烷在较低的N/P比下与siRNA形成稳定且有效的转染纳米复合物，这表明所开发的超分子载体具有高基因负载能力。我们的研究结果表明，转染复合物的生化性质取决于聚轮烷轴的结构和穿线效率，这进一步影响转染效率。将增强的基因沉默效率和安全性与广泛研究的用作siRNA递送载体的聚乙二醇基聚轮烷、聚乙烯亚胺（一种金标准）和脂质体转染试剂（一种商业标准）进行了比较。
