Low-Dimensional Materials for Antimicrobial Treatment

The escalating threat from antimicrobial resistance (AMR) has created an urgent need for non-drug based, next generation treatment methods. One field that has gained considerable interest in combatting AMR is low-dimensional materials (LDMs). One rising star within LDMs used for medical applications is black phosphorus nanoflakes (BPNFs), which have shown promising antitumor and tissue regenerative properties. While showing great biomedical properties, previous studies into BPNFs have relied on using external stimuli, such as light irradiation. This thesis explores the potential of BPNFs to act as a broad-spectrum antimicrobial agent without requiring the use of external stimulation. In the first experimental chapter, chapter 3, BPNFs were used as an antimicrobial surface coating for a range of medically relevant surfaces, such as titanium implants and bandages. In the absence of light, the BPNF coating was effective against multiple different bacterial and fungal species with varying levels of drug resistance within just 2 hours. The BPNF coatings were able to generate ROS at a high enough concentration to induce fatal damage to microbial cells, while maintaining low cytotoxicity toward mammalian cells. This chapter showcases the practical utility of BPNFs as a coating for medically relevant surfaces, offering a promising pathway for their use as an antimicrobial agent. Chapter 4 describes a more fundamental investigation into the interaction between BPNFs and model microbial cells using a range of microscopic and spectroscopic techniques. Importantly, synchrotron source macro-attenuated total reflection-Fourier transform infrared (ATR-FTIR) microspectroscopy was conducted to characterise chemical variations of microbial biofilms, as well as any changes induced by BPNFs in the absence of light at a molecular level. This study confirms the ROS-induced damage observed in chapter 3, as well as showing damage to the phospholipid cell membrane. Gaining better insight into the antimicrobial mechanism of BPNFs without light irradiation is vital for the future implementation. Chapter 5 explores the integration of BPNFs into eutectogels as a potential wound treatment gel. The eutectogel was comprised of a deep eutectic solvent (choline chloride-glycerol) and cellulose network. Since eutectogels have a minimal/limited water and free oxygen content, the degradation of BPNFs was slowed down. The BPNF-loaded eutectogels were able to show a strong antimicrobial response without any external stimuli. For the BP-loaded eutectogels, the antimicrobial efficiency after 28 days was still >80%, which is higher than typically seen from BPNFs stored in different solvents (<50% cell death). The drug delivery potential of the eutectogel was further highlighted by loading the gels with different known antimicrobial agents, including silver nanoparticles, and commercially available antiseptics, antibiotics and antifungal drugs, which all showed a strong antimicrobial response (>90% cell death). This chapter not only provided a practical application for antimicrobial BPNFs, but it also highlighted the eutectogels as promising drug delivery vehicles, capable of delivering a range of antimicrobial compounds effectively. Overall, this thesis represents a significant advancement in the understanding and utilisation of BPNFs as an antimicrobial nanomaterial. By leveraging the broad-spectrum antimicrobial properties of BPNFs without relying on light activation, this research offers promising solutions to combat AMR and address unmet medical needs. The practical applications of BPNFs in antimicrobial coatings and wound dressings highlight their potential as next-generation antimicrobial agents, advancing antimicrobial therapy and combatting the global threat of AMR.<p></p>