Nanomaterial-Based Strategies to Combat Antibiotic Resistance: Mechanisms and Applications

Abstract

The rapid rise of antibiotic resistance has become a global health crisis, necessitating the development of innovative strategies to combat multidrug-resistant (MDR) pathogens. Nanomaterials have emerged as promising tools in this fight, offering unique physicochemical properties that enhance antibiotic efficacy, overcome resistance mechanisms, and provide alternative therapeutic approaches. This review explores the diverse nanomaterial-based strategies used to combat antibiotic resistance, focusing on their mechanisms of action and practical applications. Nanomaterials such as metal nanoparticles, carbon-based nanomaterials, and polymeric nanostructures exhibit antibacterial properties through various pathways, including the generation of reactive oxygen species (ROS), disruption of bacterial membranes, and enhancement of antibiotic delivery. Additionally, the ability of nanomaterials to bypass traditional resistance mechanisms, such as biofilm formation and efflux pumps, has been demonstrated in numerous studies. This review also discusses the synergistic effects observed when nanomaterials are combined with conventional antibiotics, leading to increased bacterial susceptibility and reduced required dosages. By highlighting the recent advancements and clinical applications of nanomaterial-antibiotic combinations, this paper provides a comprehensive overview of how nanomaterials are reshaping the future of antibacterial therapies. Future research directions and challenges, including toxicity and scalability, are also addressed to guide the development of safer, more effective nanomaterial-based antibacterial treatments.

Keywords: antibiotic resistance; combatting multidrug-resistant bacteria; metal nanoparticles for infection control; nanomaterial-based antibacterial strategies; nanotechnology in antibiotic delivery.

Figure 1

The development stages of a surface-associated biofilm. Reprinted/adapted with permission from Ref [31]. 2024, Ho Yu Liu et al.

Figure 2

Role of the maintenance of lipid asymmetry (Mla) complex in the asymmetric distribution of LPSs and PLs in the outer and inner leaflets of a Gram-negative OM. In Gram-negative bacteria, the inner membrane (IM) consists of a symmetric phospholipid (PL) bilayer, whereas the outer membrane (OM) is asymmetric, with lipopolysaccharides (LPSs)/lipooligosaccharides (LOSs) exclusively occupying the outer leaflet and PLs confined to the inner leaflet. The maintenance of lipid asymmetry is orchestrated by the Mla complex, a six-component protein system in Acinetobacter baumannii, which is organized into three distinct units. The Mla complex consists of three main units: MlaA (A), MlaC (C), and MlaBDEF (B, D, E, and F). MlaA is positioned in the outer membrane (OM), MlaC is situated in the periplasm, and the MlaBDEF complex is located in the inner membrane (IM). The distinct structural properties of MlaA allow it to function similarly to a vacuum, extracting mislocalized phospholipids (PLs) from the outer leaflet of the outer membrane (OM). These mislocalized PLs are transferred to MlaC, which transports them to the PL binding site of the MlaBDEF complex, which faces the periplasm. The movement of PLs through the inner membrane (IM) occurs via the transmembrane domains of MlaD and MlaE, as shown by the dotted lines. The selective transport of PLs through the MlaBDEF complex is governed by specific residues: Leu153/Leu154 (yellow balls) at the periplasmic end, and R47, R14, and R234 (red balls) near the cytosolic end. ATP-binding sites are located on the MlaF subunits, near the interface with MlaE-F. The PL transport route within the MlaBDEF complex is bilaterally symmetrical, allowing PLs to pass through either path without preference. Once at the cytosolic side of MlaBDEF, the PLs move into the cytosolic leaflet of the IM, where they are balanced across both leaflets with the assistance of biogenic membrane flippases [87].

Figure 3

Diagrammatic representation of photosensitive polymeric nanocarriers: photosensitivity mechanisms, functionalized nanocarriers, targeted delivery, and controlled drug release [116].

Figure 4

Mechanism of nanoparticle (NP)-mediated antibiotic delivery. NPs enhance the efficacy of conventional antibiotics (Ab) by targeting resistant microorganisms, providing dual mechanisms of action: the bactericidal effect of Ab and the antibacterial properties of NPs, leading to increased bacterial cell death. NPs disrupt the cell wall, membrane, mitochondria, and enzymes, and damage proteins, inhibit efflux pumps, and generate reactive oxygen species (ROS) to induce oxidative stress [135].