Research

Life Sciences & Biotechnology

Title :	Comparative and synergistic studies of Biogenic Zinc Oxide Nanoparticles loaded in combination with 5-Fluorouracil (5-FU) and its mechanism in cell death pathways in colon cancer
Area of research :	Life Sciences & Biotechnology
Principal Investigator :	Dr. SRINIVAS PATNAIK, Kalinga Institute Of Industrial Technology (Kiit), Odisha
Timeline Start Year :	2024
Timeline End Year :	2027

Details

Executive Summary :

Chemotherapy for colon cancer usually involves a combination of drugs, such as 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and irinotecan. The side effects of chemotherapy can include nausea, vomiting, fatigue, hair loss, an increased risk of infection and the severity is high with respect to age and health condition/s. Green nanoparticle synthesis for cancer therapy is the use of metal oxide nanoparticles loaded with plant extracts. These biogenic nanoparticles have been shown to have anticancer activity against various types of cancer cells. Additionally, biogenic nanoparticles can enhance the efficacy of chemotherapy and reduce their side effects. Specifically in India, Swertia chirayita has long been used as a treatment option to treat a variety of ailments by traditional healers. In the present investigation, we would like to use Biogenic Zinc Oxide Nanoparticles loaded with Swertia chirayita Leaf Extract in Colorectal Cancer Cells alone or in combination with 5-Fluorouracil (5-FU) using in vitro and preclinical models. Increasing evidences suggests that biogenic nanoparticle alone or in combination with chemotherapeutic drug are very effective in killing cancer cells, less toxic to normal cells and presumably less prone to drug resistance that is yet to establish. Looking at our previous data and other research evidences, we hypothesize that Biogenic Zinc Oxide Nanoparticles in combination with 5-FU will regulate cell death in cancer cells and have significant effect on AKT/WNT/beta catenin pathways. Our previous research work on Zinc oxide nanoparticles (ZnO-NPs), were synthesized from ethanolic and methanolic extract of Swertia chirayita leaves. ZnO-NPs were characterized by techniques such as UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron Microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). These analysis confirmed the quality of the nanoparticles and its stability. Biological analysis of the ZnO-NPs showed anti-cancer activities by using cytotoxicity assays [MTT assay and acridine orange (AO) staining] which confirmed the cell death due to apoptosis. Gene expression analysis was performed in EMT and cell cycle regulator genes by quantitative real-time PCR (qRT-PCR) in colorectal cancer (CRC) cells (HCT-116 and Caco-2) and control cells (HEK-293). In this research proposal we would like to study the effectiveness Biogenic Zinc Oxide Nanoparticles loaded with Swertia chirayita leaf extract along with 5-FU to check cytotoxicity in colon cancer cells. Reduction in metastasis in preclinical models, activation of AKT/WNT/beta catenin pathways leading to the regulation of EMT and anti-cancer property on Apoptotic pathways will be the main objectives of the study.This study will define how effective can Biogenic Zinc Oxide Nanoparticles in combination loaded with 5-FU in combating colon cancer cells.

Co-PI:

Dr. Ruchi Mittal Kalinga Institute Of Medical Sciences,Kushabhadra Campus (Kiit Campus-5), Patia, Bhubaneswar,Odisha,Khordha-751024, Dr. Amrita Mishra Kalinga Institute Of Industrial Technology (Kiit), Odisha,Kalinga Institute Of Industrial Technology (Kiit), Odisha Patia, Bhubaneswar ,Odisha,Khordha-751024