Abstract
Colonic-targeted drug delivery system is widely explored to combat colon-related diseases such as colon cancer. Dicer-substrate small interfering RNA (DsiRNA) has been explored for cancer therapy due to its potency in targeting specific gene of interest. However, its application is limited by rapid degradation and poor cellular uptake. To address this, chitosan-graphene oxide (CS-GO) nanocomposite was used to deliver DsiRNA effectively into cells. Additionally, pectin was used as compatibilization agent to allow specific delivery to the colon and protect the nanocomposites from the harsh environment in the stomach and small intestine. CS-GO-DsiRNA nanocomposites were prepared by electrostatic interaction between CS and GO prior to coating with pectin. The mean particle size of CS-GO-DsiRNA-pectin nanocomposites was 554.5±124.6 nm with PDI and zeta potential of 0.47±0.19 and −10.7±3.0 mV, respectively. TEM analysis revealed smooth and spherical shape of CS-GO-DsiRNA nanocomposites and the shape became irregular after pectin coating. FTIR analysis further confirmed the successful formation of CS-GO-DsiRNA-pectin nanocomposites. Furthermore, the nanocomposites were able to entrap high amount of DsiRNA (% entrapment efficiency of 92.6±3.9%) with strong binding efficiency. CS-GO-DsiRNA-pectin nanocomposites also selectively inhibited cell growth of colon cancer cell line (Caco-2 cells) and were able to decrease VEGF level significantly. In a nutshell, pectin-coated DsiRNA-loaded CS-GO nanocomposites were successfully developed and they have a great potential to deliver DsiRNA to the colon effectively.
Highlights
Colorectal cancer is ranked as the third most common cancer worldwide and it contributes to major cause of death in Western country [1]
This indicated that Dicer-substrate siRNA (DsiRNA) has strong binding interaction with CS-graphene oxide (GO) nanocomposites and it was well protected by pectin layer. These results suggested that pectin coating did not affect the binding efficiency of anionic DsiRNA with cationic CS-GO nanocomposites or causing premature release of DsiRNA
Pectin-coated CS-GO-DsiRNA nanocomposites were successfully developed via electrostatic interaction
Summary
Colorectal cancer is ranked as the third most common cancer worldwide and it contributes to major cause of death in Western country [1]. Conventional treatments of colon cancer such as chemotherapy and radiotherapy have considerable drawbacks as they could not target cancer cells and might cause injury to healthy cells [2]. Patients on conventional treatment often develop tolerance to targeted therapy by gene mutation. An effective treatment approach by producing siRNA-based drug may target specific mRNAs despite of their cellular locations or structures of translated protein [3]. Kulisch et al [4] reported that Dicer-substrate siRNA (DsiRNA) displays excellent potency in gene silencing and is able to silence gene for longer time compared to siRNA. DsiRNA has several advantages compared to standard 21-mer siRNAs. The advantages include better selectivity of the guide strand as a consequence of Dicer processing and handoff to RNA-induced silencing complex (RISC) as well as higher potency attributed to lower effective concentration needed [5]
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