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

Abstract

PurposeA liposome-based siRNA–drug combination was evaluated as a potential therapeutic strategy to improve the curative effect.MethodsA 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).ResultsTf-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.ConclusionThese 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.

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820

“…SN38 is an active metabolite of the first-line drug irinotecan, with strong anti-tumor effects. However, due to the limited water solubility, unstable properties, drug resistance, and adverse reactions of SN38, its widespread clinical application is limited [ 22 ]. Nano-delivery system can increase the solubility of SN38, reduce its toxic side effects on normal tissues, and improve anti-tumor efficacy.…”

Multi-target direct-acting SARS-CoV-2 antivirals against the nucleotide-binding pockets of virus-specific proteins

“… ( Alphs et al, 2016 ; Corena-McLeod, 2015 ) Natural Product SN 38 Anti-proliferative and anti-tumor roles by activating MAPK pathways and boosting IL-8 expression. ( Bi et al, 2018 ; Zhang et al, 2017 ) Bicuculline The antagonist of receptors of inhibitory neurotransmitter GABA and enhances calcium secretion. ( Johnston, 2013 ; Mestdagh and Wülfert, 1999 ) Columbianadin Anti-cancerous and anti-inflammatory effects by inducing necroptosis and apoptosis.…”

Research Progress of SN38 Drug Delivery System in Cancer Treatment

“… 112 siRNA combined with chemotherapeutic drugs will become a new strategy for efficient tumor treatment, with good prospects for clinical translation. Bi et al 113 prepared transferrin (Tf) liposomes co-loaded with TAT-PEG-SN38 and survivin siRNA (Tf-L-SN38/P/siRNA). This liposome was able to increase endocytosis and consequently cytotoxicity in HeLa cells, and the results of in vitro cellular experiments revealed that Tf-L-SN38/P/siRNA (IC 50 =175 nM) exhibited stronger cytotoxicity compared with Tf-L-SN38 (IC 50 =2.03 μM) and SN38 (IC 50 =2.55 μM) in HeLa cells.…”