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

Abstract

Aim: To synthesize host-specific serum protein stabilized silver quantum clusters and assess their preclinical safety as potential antibacterial agents. Materials & methods: Ag-QC-NanoSera (Ag-QCNS) were synthesized using bovine, human and murine sera. Antibacterial efficacy was evaluated against E. coli (including antibiotic-resistant strain), S. aureus and P. aeruginosa. 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. Results: 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. Conclusion: Ag-QCNS demonstrate potential as next-generation host-specific nanotheranostic antibacterial agents, enhancing the safety and efficacy while combating antibiotic resistance.

GRAPHICAL ABSTRACT

Article highlights

Versatile host-specific stabilization

• Ag-QCNS were synthesized using bovine, human and murine sera, demonstrating the adaptability of the synthesis process with different biological sources.

Photoluminescent properties

• 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.

Biocompatibility & hemocompatibility

• Ag-QCNS displayed high in vitro biocompatibility in L929 normal fibroblast cells and in vivo hemocompatibility with murine RBCs.

Broad-spectrum antibacterial activity

• Ag-QCNS demonstrated concentration-dependent antibacterial efficacy against Gram-positive and Gram-negative bacteria, including E. coli, S. aureus and P. aeruginosa.

Efficacy against antibiotic-resistant strains

• The synthesized Ag-QCNS were effective against both antibiotic-sensitive and antibiotic-resistant strains of E. coli.

Mechanism of action

• The antibacterial mechanism was identified as ROS-mediated oxidative stress, causing bacterial cell membrane damage, as verified by electron microscopy.

Preclinical safety of autologous serum derived host-specific Ag-QCNS

• Acute and subacute preclinical safety of autologously derived murine Ag-QCNS was established over course of 28 days.

Potential for next generation antibacterial nanotheranostic agents

• Ag-QCNS has immense potential as next-generation host-specific nanotheranostic antibacterial agents by increasing the safety of antibacterial therapy and combating antibiotic-resistance.

Keywords: :

• antibacterial agent
• antibiotic resistance
• bacterial cell death
• host-specific
• membrane damage
• preclinical safety
• silver nanoclusters

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17435889.2024.2374231

Acknowledgments

Authors sincerely acknowledges R Das and M Jamwal at the Department of Hematology, PGIMER Chandigarh, for assisting with obtaining of human serum for the study. E. coli^KRes was received as a kind gift from S Sinha (INST, Mohali). All the other microbial cultures were procured from IMTECH, Chandigarh.

Author contributions

K Sood: conceptualization, data curation, formal analysis, investigation, methodology, validation, visualization, writing-original draft, writing-review and editing.

A Shanavas: conceptualization, funding acquisition, project administration, resources, supervision, visualization, writing-review and editing.

Financial disclosure

K Sood would like to acknowledge DST-INSPIRE (IF-180560) for her PhD fellowship. A Shanavas would like to acknowledge the Department of Biotechnology, Government of India for funding under IYBF scheme (HRD-17011/3/2023-HRD-DBT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The serum sample from a healthy human volunteer with informed written consent was obtained after necessary approvals from the Institute Ethics Committee (Approval No. PGI/IEC/2020/000787) of PGIMER Chandigarh as per ICMR (Indian Council of Medical Research) guidelines. All the animal experimentation were conducted in accordance with the guidelines approved by the Institutional Animal Ethics Committee at IISER Mohali (IISERM/SAFE/PRT/2020/001).The necessary approvals required from the institutional biosafety committee of INST, Mohali were procured.

Additional information

Funding

K Sood would like to acknowledge DST-INSPIRE (IF-180560) for her PhD fellowship. A Shanavas would like to acknowledge the Department of Biotechnology, Government of India for funding under IYBF scheme (HRD-17011/3/2023-HRD-DBT).