Neerooa Bibi Noorheen, Haleema Mooneerah (2024) Anticancer potential of metal and metal oxide nanoparticle in combination with Cisplatin and 5-Fluorouracil for colorectal cancer treatment. Masters thesis, Sunway University.
Full text not available from this repository.Abstract
Colorectal cancer (CRC) is the second deadliest cancer type globally, necessitating effective treatments to reduce its burden. Chemotherapeutic drugs are common in cancer treatment; however, their side effects cause patients’ discomfort and immense pain. Nanoparticles (NPs) have gained attention for their anti-cancer properties and synergistic effects with chemo drugs, however, there is a knowledge gap when it comes to understanding and evaluating the safety and toxicity of these NPs to human cells, organs and human as a whole thus the need to research ways to make NPs more biocompatible and effective. The NPs used in this study were synthesised by our collaborators including among them new metal complex NPs such as nickel-doped zinc NPs. In this study, we tested 14 newly synthesised metal and metal oxide NPs against colorectal cell lines (HCT116 and HT-29) in 2D and 3D spheroid models, examining their anti-cancer ability and their synergy with cisplatin or 5-Fluorouracil (5-FU). Nickel oxide and Nickel: Zinc (Ni:Zn) NPs demonstrated promising selectivity and anticancer activities for the first time. In 2D models, IC50 (inhibitory concentration that causes 50% cell death) for Nickel oxide and Ni:Zn NPs against HCT116 were 30.56 and 16.73 μg/ml, respectively, while in HT-29, the IC50 were 4.51 and 1.16 μg/ml, respectively. However, the efficacy of NPs was restricted in 3D tumour models. In combination with cisplatin or 5-FU, sub-inhibitory Nickel oxide and Ni: Zn NPs showed synergism in most models, except HT-29 3D. Cytotoxicity tests on normal cell lines, CCD 112 (colon), HUVEC (vascular endothelia), and NHDF (dermal fibroblasts), showed relatively lower IC50 for NPs compared to cancer cells except for slight cytotoxicity observed in HUVEC treated with Nickel oxide NPs and in CCD112 treated with Ni: Zn NPs. Mechanistic studies revealed significant reactive oxygen species (ROS) production in HT-29 cells treated with Nickel oxide NPs only. Nickel oxide NPs combined with cisplatin and 5-FU and Ni: Zn NPS combined with cisplatin showed significant release of superoxide (SO) against HCT116 cells. HT-29 cells treated with nickel oxide NPs combined with cisplatin and all combinations of Ni: Zn NPs has shown a significant release of SO. From the apoptosis and necrosis assay, HCT116 treated with Nickel oxide NPs and its combination has shown a significant apoptotic effect while only the combinations of Ni: Zn NPs showed a significant apoptotic effect. Nickel oxide NPs, cisplatin and Nickel oxide NPs combined with 5-FU as well as Ni: Zn NPs only, Ni: Zn NPs cisplatin and 5-Fu was able to lowered the mitochondrial membrane potential (MMP) in HCT116. Overall, our study highlights the anti-cancer action and potential synergistic effects of newly synthesised Nickel oxide and Ni: Zn NPs with chemotherapeutic drugs, Cisplatin and 5-FU. These NPs warrant further modifications to improve their cancer-targeting specificity and cytotoxicity. Their potentials to be developed into nanocarriers should also be explored.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | colorectal cancer; Cisplatin; 5-fluorouracil; nickel oxide nanoparticles; nickel-doped zn nanoparticles; anti-cancer effects; combination treatment; synergism |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RS Pharmacy and materia medica |
| Divisions: | Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] |
| Depositing User: | Ms Yong Yee Chan |
| Date Deposited: | 29 Jul 2025 05:46 |
| Last Modified: | 29 Jul 2025 05:46 |
| URI: | http://eprints.sunway.edu.my/id/eprint/3245 |
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