Mannose-functionalized Nano-Therapeutics: A targeted strategy for combating bacterial infections

Bacterial infections continue to pose a severe global health risk, which is compounded by the emergence of multidrug-resistant strains and the protective nature of biofilms. Conventional antibiotic therapies are frequently proven ineffective because of the challenges associated with bacterial invasion mechanisms and drug delivery mechanisms. Mannose-functionalized therapies have emerged as promising strategies for targeted drug delivery, emphasizing the interaction between mannose moieties and particular receptors or bacterial adhesins. Mannosylation increases drug targeting and accumulation at the site of infection, which enhances biofilm penetration and promotes macrophage-targeted drug administration via receptor-mediated endocytosis. This review examines both natural and synthetic mannosylation methods in nanocarriers, focusing on design, including chemical conjugation and enzymatic glycosylation, while detailing current progress and applications in nanodrug delivery systems, including liposomes, nanoparticles, micelles, and hydrogels, in antibacterial therapies. Mannose-modified systems demonstrate enhanced effectiveness in combating infections induced by pathogens such as E. coli, Klebsiella pneumoniae , and Mycobacterium tuberculosis. The strong binding affinity of mannose derivatives to bacterial adhesins, particularly Fim H, is further supported by in silico studies. The use of mannosylated drug carriers reduces systemic toxicity and antibiotic resistance while increasing therapeutic efficacy. Despite promising preclinical findings and ongoing patent developments, issues with stability, scalability, and regulatory procedures still exist. However, mannosylation offers a promising carbohydrate-based approach to targeted antibacterial therapy, particularly in the fight against bacterial infections that are resistant to multiple drugs.