Helal F Hetta, Fawaz E Alanazi, Hanan Alshareef, Ghareb M Soliman, Sultan A Almadi, Ageel F Aljuhani, Salwa Qasim Bukhari, Zinab Alatawi, Noura H Abd Ellah, Ali M Atoom, Mahmoud El-Maghrabey, Yasmin N Ramadan
Hypervirulent and multidrug-resistant Klebsiella pneumoniae represents a dual threat to global health, combining aggressive virulence with resistance to last-line antibiotics. Conventional therapies are failing, leaving an urgent need for disruptive approaches. Nanotechnology offers transformative solutions by enabling targeted drug delivery, dismantling biofilms, restoring antibiotic potency, and introducing novel modalities such as phage-nanoparticle hybrids and CRISPR-based nanoplatforms. This review synthesizes recent advances in metal-, polymer-, and lipid-based nanostructures designed to combat hvKp, highlighting mechanisms of action, synergistic combinations with antibiotics, and innovative theranostic systems. We also critically examine translational challenges, including reproducibility, safety, and regulatory uncertainty, while outlining future opportunities for precision nanomedicine through smart nanoplatforms, nano-enabled diagnostics, and AI-driven design. By integrating efficacy with safety and clinical feasibility, nanotechnology holds promise to reshape the therapeutic landscape for hvKp and MDR pathogens and contribute to broader strategies against antimicrobial resistance.