已发表论文

Aurora-A 抑制剂 XY-4 和 Bcl-xl siRNA 的共递送在黑素瘤治疗中增强了抗肿瘤效力

 

Authors Duan X, Mu M, Yan J, Bai L, Zhong L, Zhu Y, Pan H, Zhang M, Shi J

Received 30 July 2017

Accepted for publication 7 December 2017

Published 9 March 2018 Volume 2018:13 Pages 1443—1456

DOI https://doi.org/10.2147/IJN.S147759

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun

Background: The newly synthesized Aurora-A kinase inhibitor XY-4 is a potential anti-cancer agent, but its hydrophobicity and limited efficiency restrict further application. Nanotechnology based combined therapy provides an optimized strategy for solving these issues.
Methods: In this study, the newly synthesized Aurora-A kinase inhibitor XY-4 and Bcl-xl targeted siRNA were co-delivered by cationic liposomes, creating an injectable co-delivery formulation. The anti-cancer ability and mechanisms of XY-4/Bcl-xl siRNA co-loaded cationic liposomes were studied both in vitro and in vivo.
Results: The prepared liposomes had a mean particle size of 91.3±4.5 nm with a zeta potential of 38.5±0.5 mV and were monodispersed (Polydispersity index =0.183) in water solution, with high drug loading capacity and stability. Intriguingly, the positive charges of co-delivery liposomes not only facilitated gene delivery, but also obviously enhanced drug uptake. The XY-4/Bcl-xl siRNA co-loaded cationic liposomes demonstrated enhanced anti-cancer effects on B16 melanoma cells in vitro by activation mitochondrial apoptosis pathway. Moreover, intratumoral injection of this co-delivery formulation efficiently inhibited the growth of a B16 melanoma xenograft model in vivo.
Conclusion: By co-delivering Aurora-A kinase inhibitor XY-4 and Bcl-xl targeting siRNA in a nanoformulation, our study supplied a potential combination strategy for melanoma therapy.
Keywords: RNA interference, Aurora-A kinase inhibitor, liposome, co-delivery, melanoma, apoptosis