Graphene oxide functionalized with chitosan based nanoparticles as a carrier of siRNA in regulating Bcl-2 expression on Saos-2 & MG-63 cancer cells and its inflammatory response on bone marrow derived cells from mice

Abstract

Presently, quite a lot of research that are being carried out to find a potential cure for cancer and many had made to clinical trial stage as well. In the present study, we focus on use of a novel graphene oxide functionalized chitosan nanoparticle targeting Saos-2 and MG-63 osteosarcoma cells. The graphene oxide chitosan nanoparticles were loaded with siRNA, studied for in vitro release with varying concentration & pH, and fitted to peppas model. MTT & ROS assay was used to evaluate biocompatibility of carrier and qPCR to study the inflammatory responses in particular checking gene expression of IL-6, TGF-ß, TNF-α in both RAW 264.7 and bone marrow derived macrophages. The results of study showed that release of siRNA were in a controlled fashion and effective at acidic pH that prevails on tumor site. The material was biocompatible and effective in case of Saos-2 osteosarcoma cells with a viability of 0.4±0.43 and 0.49±0.53 in case of MG-63 cells when treated with highest concentration of 100µl siRNA compared to untreated cells that were in range of 0.64±0.67 in Saos-2 and 0.61±0.63 in MG-63 cells. The results of expression of inflammatory cytokines IL-6, TGF-β & TNF-α showed negligible amount compared to control group serving the purpose of an effective carrier targeting tumor cells. Highlights  Graphene oxide functionalized chitosan nanoparticle loaded with siRNA targeting Saos-2 and MG-63 osteosarcoma cells exhibited a controlled release.  Effective release of siRNA on cancer cells and destruction of the same.  No inflammation observed when treated with RAW and Bone Marrow derived macrophages derived from mice models.

Cytotoxic and apoptotic effect of nanoclinoptilolite on canine osteosarcoma cell lines

“…Almutairi et al (4) showed that chitosan-coated raloxifene reduced cell proliferation more effectively than the free drug and induced apoptosis in human lung and liver cancer cells. Saravanabhavan et al (29) reported that the chitosan carrier system did not cause any toxicity to normal osteoblast cells or degrade their viability. Chitosan nanoparticles were demonstrated to directly cause cell apoptosis by inducing intracellular ROS-mediated mitochondrial damage and ER stress in a study by Jiang et al (15) evaluating their effects on hepatocellular carcinoma cells based on endoplasmic stress and ROS-mediated mitochondrial damage.…”

“…In the field of healthcare, nanodrug formulations can easily move across the blood-brain barrier and be used for therapeutic purposes due to their very small size (3,4,8,15,29). Preliminary studies on the use of nanoproducts have been performed in cell cultures and then performed on experimental animals.…”

Graphene Oxide Nanoparticles Induce Apoptosis in wild-type and CRISPR/Cas9-IGF/IGFBP3 knocked-out Osteosarcoma Cells

“…Previous studies have shown that exposure to GO results in low levels of toxicity in malignant cells such as adenocarcinoma and fibrosarcoma. In the last years, research on the use of GO on OS cells has triggered a number of platforms and stimulated ideas with new aspects that can be tackled in this decade [15][16][17][18][19][20][21][22]. Substantially, there is a tremendous need to establish new therapeutic strategies for the treatment of OS for the third decade of the 21 st century.…”

“…This aspect was evident in the increased rate of apoptosis, ROS, and morphological changes observed in the osteosarcoma cell lines (SAOS2 and U2OS) compared to the standard osteoblast cell line (hFOB1. 19).…”

<p>Design and Characterization of Chitosan-Graphene Oxide Nanocomposites for the Delivery of Proanthocyanidins</p>

“…6 Nanoparticles have mainly been used for the simultaneous release of genes and chemotherapy drugs. [12][13][14] Although such carriers are useful for the transport of chemical compounds, no studies have immobilized phytodrugs on GO-CS nanoparticles.…”