Effects of sucrose ester structures on liposome-mediated gene delivery.

Unlabelled: Sucrose esters (SEs) have great potential applications in gene delivery because of their low toxicity, excellent biocompatibility, and biodegradability. By using tripeptide-based lipid (CDO) as a model lipid and SEs as helper lipids, a series of liposomes were prepared. The SEs with hydrophilic-lipophilic balance (HLB) values of 1, 6, 11, or 16 and the fatty acids of laurate, stearate, or oleate were used in the liposomes. We investigated the effect of HLB values of SEs and fatty acid types on gene transfection efficiency and toxicity of liposomes. The results showed that transfection efficiencies of the liposomes containing SEs with HLB value of 6 were superior to other liposomes in HeLa, MCF-7, NCI-H460, and A549 tumor cells. For the same HLB value, liposomes of laurate SEs were preferable to transfect cells compared to SEs of stearate and oleate. The liposomes with SEs showed higher cellular uptake than liposome without SEs (LipoCDO). LipoL12-6/Luc-siRNA treatment on tumor-bearing mice exhibited about 60% in vivo gene silencing of luciferase, and LipoL12-6 could mediate IGF-1R siRNA to greatly inhibit tumor growth. Moreover, liposomes with SEs revealed remarkably low toxicity in vitro and in vivo. The illustration of SE structures on gene delivery will promote the use of SEs for clinical trials of liposomes.

Statement Of Significance: This article is the first to study the effects of various chain lengths and hydrophilic-lipophilic balance (HLB) of sucrose esters (SEs) on gene transfection efficiency and safety of liposomes for gene delivery. The in vitro delivery of pDNA and siRNA by lipoplexes against HeLa, MCF-7, NCI-H460, and A549 tumor cells showed that the lipoplexes could lead to better transfection and lower cytotoxicity after the addition of SEs. SEs with shorter chain and a median HLB value could provide the liposomes with much higher gene transfection efficiency than others. The in vivo delivery of siRNA to tumor-bearing mice further confirmed that liposome containing laurate SE (LipoL12-6) could be a potential therapeutic vector, as it delivered siRNA to silence nearly 60% of the luciferase in tumors and also greatly inhibited the tumor growth. Therefore, the addition of SEs to liposomes proved to be relatively safe in vitro and in vivo. These preliminary results demonstrated that SEs show great potential for constructing controlled-release systems for gene delivery. The readers will get insights into a series of gene vectors and deepen their understanding about gene delivery.