Advancement in neutrophil-based drug delivery systems.

Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation or infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, the system also faces several challenges requiring resolution, such as difficulties in cell collection and preservation, the need for stability optimization, difficulties for large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable the precise delivery of anti-cancer drugs to tumor sites, potentially disrupting the immunosuppression of tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, they can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems, such as the development of novel nanomaterials and optimization of targeting ligand affinity, aim to improve the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applications, aiming to offer key insights for the development of novel drug delivery systems and thus advancing precision medicine and targeted therapy.