Infection microenvironment-related antibacterial nanotherapeutic strategies

The emergence and spread of antibiotic resistance is one of the biggest challenges in public health. There is an urgent need to discover novel agents against the occurrence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The drug-resistant pathogens are able to grow and persist in infected sites, including biofilms, phagosomes, or phagolysosomes, which are more difficult to eradicate than planktonic ones and also foster the development of drug resistance. For years, various nano-antibacterial agents have been developed in the forms of antibiotic nanocarriers. Inorganic nanoparticles with intrinsic antibacterial activity and inert nanoparticles assisted by external stimuli, including heat, photon, magnetism, or sound, have also been discovered. Many of these strategies are designed to target the unique microenvironment of bacterial infections, which have shown potent antibacterial effects in vitro and in vivo. This review summarizes ongoing efforts on antibacterial nanotherapeutic strategies related to bacterial infection microenvironments, including targeted antibacterial therapy and responsive antibiotic delivery systems. Several grand challenges and future directions for the development and translation of effective nano-antibacterial agents are also discussed. The development of innovative nano-antibacterial agents could provide powerful weapons against drug-resistant bacteria in systemic or local bacterial infections in the foreseeable future.