Nanomedicines as a cutting-edge solution to combat antimicrobial resistance

Abstract

Antimicrobial resistance (AMR) poses a critical threat to global public health, necessitating the development of novel strategies. AMR occurs when bacteria, viruses, fungi, and parasites evolve to resist antimicrobial drugs, making infections difficult to treat and increasing the risk of disease spread, severe illness, and death. Over 70% of infection-causing microorganisms are estimated to be resistant to one or several antimicrobial drugs. AMR mechanisms include efflux pumps, target modifications (e.g., mutations in penicillin-binding proteins (PBPs), ribosomal subunits, or DNA gyrase), drug hydrolysis by enzymes (e.g., β-lactamase), and membrane alterations that reduce the antibiotic's binding affinity and entry. Microbes also resist antimicrobials through peptidoglycan precursor modification, ribosomal subunit methylation, and alterations in metabolic enzymes. Rapid development of new strategies is essential to curb the spread of AMR and microbial infections. Nanomedicines, with their small size and unique physicochemical properties, offer a promising solution by overcoming drug resistance mechanisms such as reduced drug uptake, increased efflux, biofilm formation, and intracellular bacterial persistence. They enhance the therapeutic efficacy of antimicrobial agents, reduce toxicity, and tackle microbial resistance effectively. Various nanomaterials, including polymeric-based, lipid-based, metal nanoparticles, carbohydrate-derived, nucleic acid-based, and hydrogels, provide efficient solutions for AMR. This review addresses the epidemiology of microbial resistance, outlines key resistance mechanisms, and explores how nanomedicines overcome these barriers. In conclusion, nanomaterials represent a versatile and powerful approach to combating the current antimicrobial crisis.

Fig. 1. Representations of the mechanism of AMR in microbes.

Fig. 2. Consequences of AMR in healthcare sectors (A). List of different approaches to combat AMR from nanotechnology to public awareness and education (B).

Fig. 3. Several mechanisms of nanomaterials to eliminate AMR.

Fig. 4. Different nanocarriers used for the delivery of antimicrobial agents (figure prepared using https://Biorender.com).

Fig. 5. The CuNP-based nanocarrier's mode of action. (a) Zone of inhibition (b) and biofilm reduction (c) of S. aureus and E. aerogenes after treatment with CuO NS (figures reproduced from ref. , Copyright© 2024, Elsevier).

Fig. 6. Gold nanostructures for targeting S. aureus. SEM and TEM images of gold nanostructures treated S. aureus (A). Therapeutic effects of gold nanostructures on MRSA infections in vivo, reducing bacterial counts in a mouse skin infection model (B) and improving survival rates in a bacteremia model (C) when combined with oxacillin and vancomycin (figures reproduced from ref. with permission, Copyrights© 2018 Wiley).

Fig. 7. Schematic representation of structure of LipoFFA and its incubation with H. Pylori (upper figure). TEM and SEM images of H. Pylori exposed with LipoLLA (lower figures) (figures reproduced from ref. , Copyright© 2015 Jung et al., PLOS One).

Fig. 8. FEG-SEM images of CUR loaded polymeric nanoparticles (a). Mean values of log₁₀ (CFU mL⁻¹) of planktonic culture (b) and uptake of CUR loaded polymeric nanoparticles by the triple species biofilms (c) (figures reprinted with permission from ref. , Copyright© 2017).