Autologous serum protein stabilized silver quantum clusters as host-specific antibacterial agents

<b>Aim:</b> To synthesize host-specific serum protein stabilized silver quantum clusters and assess their preclinical safety as potential antibacterial agents. <b>Materials &amp; methods:</b> Ag-QC-NanoSera (Ag-QCNS) were synthesized using bovine, human and murine sera. Antibacterial efficacy was evaluated against <i>E. coli</i> (including antibiotic-resistant strain), <i>S. aureus</i> and <i>P. aeruginosa</i>. Biocompatibility, hemocompatibility and antibacterial mechanism were also investigated. Preclinical safety and biodistribution of autologous Ag-QCNS were assessed in BALB/c mice over 28 days. <b>Results:</b> Ag-QCNS showed high biocompatibility, hemocompatibility and high antibacterial activity at ∼12.72 μg/ml Ag equivalent. Intracellular ROS and bacterial membrane damage were confirmed as antibacterial mechanism. Ag-QCNS were established as preclinically safe. <b>Conclusion:</b> Ag-QCNS demonstrate potential as next-generation host-specific nanotheranostic antibacterial agents, enhancing the safety and efficacy while combating antibiotic resistance. Ag-QCNS were synthesized using bovine, human and murine sera, demonstrating the adaptability of the synthesis process with different biological sources. Ag-QCNS synthesized were ∼2 nm in size range and exhibited red fluorescence, allow for real-time monitoring of antibacterial activity, providing an additional diagnostic tool. Ag-QCNS displayed high <i>in vitro</i> biocompatibility in L929 normal fibroblast cells and <i>in vivo</i> hemocompatibility with murine RBCs. Ag-QCNS demonstrated concentration-dependent antibacterial efficacy against Gram-positive and Gram-negative bacteria, including <i>E. coli</i>, <i>S. aureus</i> and <i>P. aeruginosa</i>. The synthesized Ag-QCNS were effective against both antibiotic-sensitive and antibiotic-resistant strains of <i>E. coli</i>. The antibacterial mechanism was identified as ROS-mediated oxidative stress, causing bacterial cell membrane damage, as verified by electron microscopy. Acute and subacute preclinical safety of autologously derived murine Ag-QCNS was established over course of 28 days. Ag-QCNS has immense potential as next-generation host-specific nanotheranostic antibacterial agents by increasing the safety of antibacterial therapy and combating antibiotic-resistance.