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REVIEW

Emerging nanotechnology-based antimicrobials against antimicrobial-resistant gram-negative bacteria: Mechanisms, therapeutic advances, and translational challenges

Tolutope Adebimpe Oso1,2 ,  Olalekan John Okesanya1,3,4 ,  Uthman Okikiola Adebayo1,4,5,6* ,  Khalifat Boluwatife Obadeyi1 ,  Oluwatobi Babajide Ayelaagbe1 ,  Clement Ngele Chukwu1 ,  Abdulrahman Kayode Yahaya1 ,  Kabiru Olalekan Tajudeen1 ,  Ezekiel Onyemaechi Enwose1 ,  Olaoluwa Joseph Oso7 ,  Mohamed Mustaf Ahmed8 ,  Anjola Jesu Joy Oso9 ,  Don Eliseo Lucero-Prisno III10,11,12
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1 Department of Medical Laboratory Science, Neuropsychiatric Hospital, Aro, Abeokuta, Nigeria
2 Department of Medical Laboratory Science, McPherson University, Seriki Sotayo, Ogun State, Nigeria
3 Department of Public Health and Maritime Transport, Faculty of Medicine, University of Thessaly, Volos, Thessaly, Greece
4 Department of Public Health, Daffodil International University, Dhaka, Bangladesh
5 Department of Medical Laboratory Services, Federal University of Health Sciences Teaching Hospital, Ila-Orangun, Osun State, Nigeria
6 Department of Public Health, Faculty of Medicine and Health Sciences, Hormuud University, Mogadishu, Banaadir, Somalia
7 Department of Nursing Science, College of Health Sciences, Bowen University, Iwo, Osun State, Nigeria
8 School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
9 Department of Architecture, Bells University of Technology, Ota, Ogun State, Nigeria
10 Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, England, United Kingdom
11 Research and Innovation Office, Southern Leyte State University, Sogod, Southern Leyte, Philippines
12 Center for Research and Development, Cebu Normal University, Cebu, Philippines
BMT, 160 https://doi.org/10.12336/bmt.25.00160
Submitted: 29 August 2025 | Revised: 22 June 2026 | Accepted: 6 July 2026 | Published: 13 August 2026
© 2026 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
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Abstract

Antimicrobial resistance in Gram-negative bacteria (GNB) represents a significant global health threat, as growing resistance diminishes the effectiveness of standard antibiotics. Due to their unique physicochemical properties, multifunctionality, and ability to overcome conventional resistance mechanisms, nanotechnology-based antimicrobials have emerged as promising alternative or adjunctive therapeutic strategies. This systematic review outlines recent developments in nanotechnology-based antimicrobial strategies targeting antimicrobial-resistant GNB, detailing their mechanisms, therapeutic applications, and translational challenges. A thorough search of PubMed, Scopus, HINARI, and Google Scholar was conducted for English-language studies published between 2014 and 2024 assessing nanotechnology-based antimicrobials against antimicrobial-resistant GNB. Reviewers independently screened titles, abstracts, and full texts using Rayyan, with disagreements resolved by a third reviewer. Data were extracted using a pretested Excel form, methodological quality was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist, and findings were narratively synthesized due to study heterogeneity. Findings showed that nanoparticles (NPs) exert bactericidal effects through the generation of reactive oxygen species, disruption of the cell membrane, inhibition of efflux pumps, interference with DNA and proteins, disruption of biofilms, and targeted drug delivery. Traditional metallic NPs, including silver, zinc oxide, copper oxide, and gold NPs, demonstrated broad-spectrum antimicrobial activity against multidrug-resistant Gram-negative pathogens. Emerging nanotherapeutic strategies, including multifunctional nanoplatforms, photothermal and photodynamic systems, stimuli-responsive nanocarriers, nanozyme-based systems, and metal-organic framework-associated platforms, showed enhanced antibacterial activity, improved biofilm penetration, and synergistic effects with conventional antibiotics. Green synthesis methods were frequently emphasized due to their sustainability and enhanced biocompatibility. However, significant translational challenges remain, including limited in vivo validation, cytotoxicity concerns, synthesis variability, scalability, regulatory barriers, and insufficient long-term safety data. This review highlights the promise of nanotechnology-based antimicrobial approaches as multifunctional therapeutic platforms against antimicrobial-resistant GNB. Further in vivo studies, standardized synthesis, toxicological assessments, and clinical research are needed to support safe and effective clinical translation.

Keywords
Nanotechnology
Antimicrobial resistance
Gram-negative bacteria
Nanoparticles
Multidrug-resistant bacteria
Funding
None.
Conflict of interest
The authors state that there are no conflicts of interest.
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