Abstract
Small interfering RNAs (siRNA) technology has emerged as a promising therapeutic tool for human health conditions like cancer due to its ability to regulate gene silencing. Despite FDA-approved, their delivery remains localized and limiting their systemic use. This study used single-walled carbon nanotubes (SWNTs) functionalized with polyethylene glycolated (PEGylated) phospholipids (PL-PEG) derivatives for systemic siRNA delivery. We developed an siRNA systemic delivery vehicle (SWNT-siRNA) by conjugating SWNT functionalized with PL-PEG containing either amine (PA) or maleimide (MA). The functionalized SWNT with a lower molecular weight of PA produced the SWNT-siRNA conjugate system with the highest stability and high siRNA loading quantity. The system delivered siRNA to a panel of tumour cell lines of different organs (i.e. HeLa, H1299 and MCF-7) and a non-cancerous human embryonic kidney 293 cells (HEK293T) with high biocompatibility and low toxicity. The cellular uptake of SWNT-siRNA conjugates by epithelial cells was found to be energy dependent. Importantly, the presence of P-glycoprotein, a marker for drug resistance, did not inhibit SWNT-mediated siRNA delivery. Mouse xenograft model further confirmed the potential of SWNT-siRNA conjugates with a significant gene knock-down without signs of acute toxicity. These findings pave the way for potential gene therapy applications using SWNTs as delivery vehicles.
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