Cell Growth Inhibition Effect of DsiRNA Vectorised by Pectin-Coated Chitosan-Graphene Oxide Nanocomposites as Potential Therapy for Colon Cancer

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-DsiRNApectin 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.

Eco-Friendly Synthesis of Biocompatible Pectin Stabilized Graphene Nanosheets Hydrogel and Their Application for the Simultaneous Electrochemical Determination of Dopamine and Paracetamol in Real Samples

“…But in the case of PT/RGO, the intensity of D/G ratio will be higher as compared to other carbon based composite materials. 35 EIS is a promising technique to study the electrochemical properties between the electrode surface and electrolyte. Fig.…”

Biomedical applications of chitosan-graphene oxide nanocomposites

“…For example, to combat colon-related diseases, Katas et al. (2017) invented a chitosan–graphene oxide–Dicer-substrate small interfering RNA (CS–GO-DsiRNA-pectin) colonic-targeted drug delivery system via electrostatic interaction.…”

Structure and Applications of Pectin in Food, Biomedical, and Pharmaceutical Industry: A Review

“…In men, it is the third most common type of cancer, and in women, the second most common type [120,121]. Conventional treatments, such as chemotherapy and radiotherapy, have considerable disadvantages, as they do not specifically target cancer cells and can cause damage to healthy cells [122]. Currently, anticancer agents of plant origin, such as curcumin, are competitors as chemotherapy alternatives.…”

“…It is observed prominence in research involving nanotherapy due to overcoming limitations associated with conventional therapeutic approaches, such as non-specificity in biodistribution, low aqueous solubility, and limited bioavailability of the asset. Lately, nanoparticles have been designed to overcome the restrictions imposed by biological barriers and offer clinical advantages over the administration of free medication in terms of flexibility in administration, toxicity, and controlled drug release capacity [122,127].…”