Colistin-Conjugated Selenium Nanoparticles: A Dual-Action Strategy Against Drug-Resistant Infections and Cancer

<b>Background/Objective</b>: Antimicrobial resistance (AMR) and therapy-resistant cancer cells represent major clinical challenges, necessitating the development of novel therapeutic strategies. This study explores the use of selenium nanoparticles (SeNPs) and colistin-conjugated selenium nanoparticles (Col-SeNPs) as a dual-function nanotherapeutic against multidrug-resistant <i>Pseudomonas aeruginosa</i>, antifungal-drug-resistant <i>Candida</i> spp., and human breast carcinoma (MCF-7) cells. <b>Methods</b>: SeNPs were synthesized and characterized using UV-Vis spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR), confirming their nanoscale morphology, purity, and stability. <b>Results</b>: The antimicrobial activity of SeNPs and Col-SeNPs was assessed based on the minimum inhibitory concentration (MIC) and bacterial viability assays. Col-SeNPs exhibited enhanced antibacterial effects against <i>P. aeruginosa</i>, along with significant downregulation of the <i>mexY</i> efflux pump gene, which is associated with colistin resistance. Additionally, Col-SeNPs demonstrated superior antifungal activity against <i>Candida albicans</i>, <i>C. glabrata</i>, and <i>C. krusei</i> compared to SeNPs alone. The anticancer potential of Col-SeNPs was evaluated in MCF-7 cells using the MTT assay, revealing dose-dependent cytotoxicity through apoptosis and oxidative stress pathways. Although MCF-7 is not inherently drug-resistant, this model was used to explore the potential of Col-SeNPs in overcoming resistance mechanisms commonly encountered in cancer therapy. <b>Conclusions</b>: these findings support the promise of Col-SeNPs as a novel approach for addressing both antimicrobial resistance and cancer treatment challenges. Further in vivo studies, including pharmacokinetics and combination therapies, are warranted to advance clinical translation.