Chemotherapy and radiation therapy have long been known as standard treatments for cancer. Despite the fact that these treatments appeared to be extremely effective against cancer cells, these non-selective therapies often lead to the failure of many biological processes, resulting in serious side effects. Recent studies have shown the capacity of nanoparticle-based treatment to target specific oncotic cells, thus overcoming these adverse side effects. The principal focus on the cytotoxic mechanism of these nanoparticles to induce apoptosis towards cancer cells makes them a promising anti-cancer agent. Zinc oxide nanoparticles (ZnO NPs) are one of the widely explored nanoparticles in cancer treatment methodology. This review outlined ZnO NP’s unique physiochemical properties including its mechanisms with an essential focus given in size- and shape-induced cytotoxicity. The initial selection process identified a total of 3,204 literature works published from 2016 to the present year in various online databases such as ScienceDirect, PubMed, NCBI, and ResearchGate. The accumulated literature expound on the unique properties of the ZnO NPs, mechanism of cytotoxicity, and cytotoxic evaluation of the ZnO NPs towards cancer cells. Throughout the extensive analysis, the data gathered from this review had reported evidence of ZnO NP’s anti-proliferative activity via different mechanisms of apoptosis-induced cytotoxicity. Smaller-sized nanoparticles appeared to be more potent than their large counterparts due to easier cell migration. The results of this review also concluded no direct correlation between the shape and cytotoxic potency, however, further studies are recommended to have a definite set of biological and exposure conditions when investigating shape-induced cytotoxicity.
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