Efficacy of cationic polymer-coated magnesium oxide nanoparticles as anti-cancer candidates

Conventional cancer therapies are frequently limited by systemic toxicity and inadequate selectivity, necessitating the development of novel therapeutic approaches. Nanotechnology has emerged as a promising platform for achieving targeted and drug-free cancer treatments. In this study, we report a drug-free anti-cancer strategy based on cationic polymer-coated magnesium oxide nanoparticles (MgO NPs). The nanocomposites (NCs) were fabricated by grafting cationic 3-acrylamidopropyl trimethyl ammonium chloride (AMPTMA)-based polymers onto 3-aminopropyltriethoxysilane (APTES)-functionalized MgO NPs, thereby integrating the cytotoxic properties of MgO, potentially mediated by reactive oxygen species (ROS) generation and Mg²⁺ ion release, with the membrane-targeting capacity of cationic polymers. Cytotoxicity assessments indicated that commercial MgO NPs exhibited minimal anti-cancer activity. While both poly-AMPTMA (PAMPTMA) homopolymer and its copolymer (PAMPTMA-<i>r</i>-BuMA) demonstrated potent cytotoxicity, they lacked selectivity, affecting both cancerous and normal cells. In contrast, the polymer-modified MgO NCs markedly enhanced cytotoxicity against cancer cell lines (A-549 half-maximal inhibitory concentrations (IC₅₀): 202 and 64 µg ml^-1; Colon-26 IC₅₀: 338 and 115 µg ml^-1) while reducing toxicity towards normal cells (human dermal fibroblast (HDF) IC₅₀: 180 and 226 µg ml^-1). Notably, the MgO-APTES-PAMPTMA-<i>r</i>-BuMA nanocomposite exhibited superior selectivity and efficacy, presumably through enhanced membrane disruption and ROS production. These findings underscore the potential of polymer-functionalized MgO NCs as a promising drug-free anti-cancer platform and contribute to the advancement of nanomedicine-based therapeutics.