Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 3 2025 05 05 313 333 Sajjad Shekarchian Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran Marzieh Eghtedardoost Arena Best Diagnostics Lab Ltd., Tehran, Iran Hannaneh Golshahi Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran Helia Behrouzfar Faculty of Veterinary Medicine, Science and Research Branch of Islamic Azad University, Tehran, Iran Zahra Fakhroueian 5 School of Chemical Engineering-Nanomedicine, College of Engineering and IPE, University of Tehran, Tehran, Iran Roya Yaraee Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran 2024 10 06 2024 11 23 Lung cancer is a leading cause of cancer deaths worldwide and new therapeutic approaches are needed. This study investigates the efficacy of a new zinc oxide-based nanomedicine in a mouse model of heterotopic lung cancer. C57BL/6 mouse model with Lewis lung carcinoma (LL2) cells was used. The mice were treated with different doses of nanodrug, cisplatin, or phosphate-buffered saline. Tumor growth, metastasis, markers for oxidative stress, and immune responses, in particular the infiltration of CD8+ T cells, were examined. The nanodrug significantly reduced tumor size, inhibited metastasis, and improved survival compared to the control group. Moreover, no significant toxic effect was observed in hematological, biochemical and histopathological analyses. Furthermore, the nanodrug altered the tumor microenvironment in favor of immune system activation by modulating the level of oxidative stress and increasing CD8+ cell infiltration. The results show that this new nanomedicine may be a candidate for an effective treatment for lung cancer. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4215 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4215/2176