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Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

Authors Bi Y, Lee RJ, Wang X, Sun Y, Wang M, Li L, Li C, Xie J, Teng L

Received 7 May 2018

Accepted for publication 8 July 2018

Published 4 October 2018 Volume 2018:13 Pages 5811—5822

DOI https://doi.org/10.2147/IJN.S173279

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Ye Bi,1 Robert J Lee,1,2 Xinyu Wang,1 Yating Sun,1 Mengqiao Wang,1 Lianlian Li,1 Chenliang Li,1 Jing Xie,1 Lesheng Teng1

1School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA

Purpose: A liposome-based siRNA–drug combination was evaluated as a potential therapeutic strategy to improve the curative effect.
Methods: A topoisomerase inhibitor SN38 prodrug was combined with a survivin siRNA through codelivery using transferrin (Tf)-L-SN38/P/siRNA. In this combination, SN38 was conjugated to the cell penetrating peptide TAT through a polyethylene glycol (PEG) linker to synthesize TAT-PEG-SN38. The amphiphilic TAT-PEG-SN38 was used as an ingredient of liposomes to improve the cellular uptake. Protamine was added to form an electrostatic complex with siRNA in the core of the liposomes. Tf was introduced to enable tumor cell targeting of liposomes (Tf-L-SN38/P/siRNA).
Results: Tf-L-SN38/P/siRNA exhibited a particle size of 148 nm and a ζ-potential of +7.8 mV. The cellular uptake and antitumor activity were dependent on Tf receptor targeting, TAT-PEG-SN38, and siRNA codelivery. Tf-L-SN38/P/siRNA was shown to be considerably more effective than liposomes carrying individual components. This combination induced potent tumor inhibition (76.8%) in HeLa cell xenograft tumor-bearing nude mice.
Conclusion: These data indicated that Tf-L-SN38/P/siRNA was an effective system for codelivery of SN38 and a survivin siRNA and that its therapeutic potential deserved further evaluation.

Keywords: SN38, survivin, siRNA, transferrin, prodrug

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