a University Institute of Radiological Sciences and Medical Imaging Technology,

The University of Lahore, Lahore, Pakistan

b Institute of Physics, The Islamia University of Bahawalpur, Bahawalpur,

Pakistan

c Department of Eastern Medicine, University College of Conventional Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

d Department of Eastern Medicine, G.C. University Faisalabad, Pakistan

e Department of Life Sciences, School of Sciences, University of Management and Technology, Lahore, Pakistan

f School of Pharmacy and Medical Sciences, Griffith University, Australia

g Department of Physics, The University of Lahore, Lahore, Pakistan

h Department of Pharmacology, College of Medicine, University of Bisha,

Bisha,61922, Saudi Arabia

i Renewable Energy and Environmental Technology Centre, University of Tabuk, Tabuk, 47913, Saudi Arabia

^jSchool of Chemistry, University of the Punjab, Lahore 54590, Pakistan

Nanocomposites, primarily consisting of metal oxide nanoparticles, have advanced drug delivery and cancer therapy. These nanoparticles are smart for biomedical relevance owing to their biocompatibility, ease of functionalization and capability to generate reactive oxygen species (ROS), which are critical for cancer treatment. This study focuses on the synthesis and characterization of TiO2 and ZnO NPs along with their nanocomposites, functionalized with polymers of polyethylene glycol (PEG) and folic acid (F.A) individually as well as nanocomposites, and loaded with anti-cancer drug Doxorubicin (DOX). The ROS generation and cytotoxic effects of samples were assessed in human liver cancer cells, demonstrating their potential to induce oxidative stress and cell apoptosis. The results showed that individual nanoparticles produced significant ROS and exhibited higher toxicity, while their composites, particularly modified PEG, F.A and DOX had reduced cytotoxicity. This indicates that the functionalizing NPs can reduce the harmful effects of ROS. Ultimately, these findings highlight the potential of nanoparticle design to enhance therapeutic efficiency while minimizing toxicity to normal tissues, contributing to more effective cancer treatment strategies.