Engineered Phage-Guided Nanotherapeutic Systems for Precision Antibacterial Therapy: Hacking Bacterial Resistance Mechanisms

Antibiotic resistance (ABR) poses a critical global public health challenge necessitating immediate action. Without prompt interventions, infections caused by antibiotic-resistant bacteria could surpass the annual mortality rates of all cancers combined by 2050. Phages are one of the most abundant biological entities on earth that specifically infect and replicate in bacterial cells and can act as potential alternatives to antibiotics. Nanotechnology provides a favorable solution to overcome various challenges linked with phage therapy. Developments in nanotechnology, including nano-encapsulation, offer solutions to various clinical as well as pharmacological challenges by improving delivery efficacy, ensuring controlled release, and protecting phages from environmental degradation and immune clearance. The synergistic actions of phage-guided targeting and the strong bactericidal potential of engineered nanocapsules (NCs) could effectively eradicate multidrug-resistant (MDR) bacteria while diminishing off-target activities. Potential applications of engineered phage-guided nanotherapeutic systems have already been explored in terms of phage/nanocarrier cocktails, enhanced antibacterial activity, effective treatment of nosocomial infections, wound healing, and disruption of bacterial biofilms. The present review focuses on comprehensively discussing the advances in phage-guided NCs along with their mechanisms in enhancing precision antibacterial therapy. In this regard, numerous in vitro and in vivo study findings have been summarized in this review. Moreover, various approaches to overcome and optimize the pharmacokinetic profiles of phage-guided NCs have been discussed.