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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