Theranostic ^99mTc-labeled vancomycin-functionalized cerium oxide nanoparticles: Antibacterial efficacy, in vitro cytotoxicity, and in vivo biodistribution studies

The rising prevalence of bacterial infections, and the limitations of conventional antibiotics, necessitates the development of advanced therapeutic strategies. While vancomycin is highly effective against gram-positive pathogens, its highly hydrophilic properties and poor tissue retention may limit its therapeutic efficacy. In this study, vancomycin-functionalized cerium oxide nanoparticles (CeO₂-VanNPs) were developed as a dual-function nanotheranostic platform for combined antibacterial therapy and radio-imaging. CeO₂ nanoparticles were synthesized via a hydroxide-mediated precipitation method and successfully conjugated with vancomycin, achieving efficient drug loading. Physicochemical characterization study and transmission electron microscopy (TEM) indicated nanoscale particle size, successful surface functionalization, and good colloidal stability. In vitro release studies demonstrated a biphasic release profile of vancomycin over 24 h. CeO₂-VanNPs exhibited enhanced antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with synergistic effects (FIC ≤ 0.5), as evidenced by reduced minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Biocompatibility assessment revealed acceptable cytotoxicity profiles and minimal hemolytic activity (<5%). Radiolabeling with technetium-99m ([^99mTc]Tc) achieved high labeling efficiency (98.68 ± 0.5%) and maintained stability for up to 8 h, enabling reliable in vivo radiotracking. Biodistribution studies of [^99mTc]Tc-CeO₂-VanNPs demonstrated preferential accumulation in inflamed tissues, indicating effective inflammation-targeting capability and good pharmacokinetic performance. These findings highlight CeO₂-VanNPs as a promising biocompatible theranostic nanoplatform with synergistic antibacterial and diagnostic potential, supporting their application in precision nanomedicine.