Chemically mediated modification of bacteriophages: Strategies, functionalities and applications in precision medicine

Bacteriophages are tiny microorganisms with remarkable specificity and versatility, contributes as promising tools in modern biomedicine due to their innate affinity for bacterial hosts. However, in order to effectively utilize their potential in advanced biomedical applications, their native structures are frequently modified to combat challenges like low stability, restricted targeting ability, and insufficient functional diversity. Although genetic engineering has been widely explored, chemically mediated modification of bacteriophages has emerged as an effective method for endowing bacteriophages than genetic modification due to its capability to utilize the functional groups present in the capsid proteins, as well as introduced non-natural moieties, to enable site-specific conjugation and functionalization with variety of therapeutic applications. Modified bacteriophages have shown great promise in antibacterial, antitumor, vaccine, gene delivery, bioimaging, and diagnostic applications, etc. Chemical conjugations play a vital role in transforming bacteriophages into multifunctional therapeutic system for next-generation precision medicine. This review summarizes the state-of-the-art advances in chemically mediated modification of bacteriophages and highlights their key benefits in enhancing therapeutic efficacy.