Platelet-phage conjugates for targeted therapy of acute bacterial pneumonia.

Abstract

Against the escalating global threat of antibiotic resistance, phages have emerged as a promising biological therapy capable of selectively lysing pathogenic bacteria. However, their rapid systemic clearance and limited tissue targeting remain major obstacles to clinical translation. Here, we develop platelet-phage conjugates (PPCs) as a biologically guided delivery platform to enhance targeted phage therapy for bacterial pneumonia. By harnessing the innate inflammatory tropism of platelets, phages are conjugated onto platelet carriers, enabling active homing to sites of infection. As early responders to inflammatory cues, platelets rapidly accumulate at infectious foci, where they sequester bacteria and facilitate microbial clearance. Leveraging these intrinsic properties, PPCs achieve precise localization within infected lung tissue. Meanwhile, the infection environment and the direct bacterial interactions also trigger platelet activation and platelet-derived microparticles release, promoting the localized release of conjugated phages. We demonstrate that PPCs significantly increased accumulation in lung infection regions, extend their circulation half-life, and effectively treat pneumonia in mice caused by bacterial infections.