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  • Title: Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy.
    Author: Bi Y, Lee RJ, Wang X, Sun Y, Wang M, Li L, Li C, Xie J, Teng L.
    Journal: Int J Nanomedicine; 2018; 13():5811-5822. PubMed ID: 30323583.
    Abstract:
    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.
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