Combating the Bloodstream Infection Cascade: Sequential Therapeutic Nanomaterials for Pathogen Elimination, Immunomodulation, and Organ Protection

Abstract Bloodstream infections (BSIs) are life-threatening systemic syndromes with a high mortality rate, characterized by a highly sequential pathophysiological progression. Although early antimicrobial and anti-inflammatory treatments have improved short-term survival rates, single-stage interventions are insufficient to reverse the high risk of long-term mortality among survivors. To address the urgent clinical need for stage-specific interventions to improve patient outcomes, nanomaterials have emerged as a highly promising platform due to their design flexibility and intelligent microenvironmental responsiveness. This Review first outlines the pathophysiological characteristics of BSIs at each stage, from the initial pathogen invasion to the final multiple-organ dysfunction, which serves as the basis for the design of nanomaterials. Then, following the progression of BSIs, the representative nanotherapeutic strategies developed in recent years for different pathological stages are systematically categorized and discussed. Finally, the review discusses the challenges confronting nanomaterials in BSI management, such as the selection of optimal treatment timing and clinical translation, and provides future perspectives on design strategies and developmental directions for nanomaterials in BSI treatment.