Immune cell-mediated nanoparticle delivery in cancer therapy: Progress and prospects of neutrophil and macrophage carriers

The efficacy of conventional nanoparticle-based drug delivery systems is often hindered by the complex tumor microenvironment, which includes abnormal vasculature, a dense extracellular matrix, and immune clearance. A promising strategy to address these challenges is the use of immune cells, such as neutrophils and macrophages, which possess inherent chemotactic properties. This review explores recent advancements in neutrophil- and macrophage-mediated nanoparticle delivery, focusing on their biological mechanisms, delivery strategies, and applications in various solid tumors. Neutrophils rapidly target acute inflammation and metastatic sites, whereas macrophages provide sustained drug release and immunomodulatory effects, making them effective in chronic tumor environments. However, these two approaches require considerable time before clinical application. Despite extensive chemical and surface modifications, nanoparticle-based delivery continues to be severely constrained by biological barriers, including abnormal vasculature, dense stroma, and heterogeneous target expression, limiting the proportion of the administered dose that reaches tumor tissues. Methods for modifying nanoparticles have nearly reached saturation, and the modification of cells used for loading and immune engineering is likely to drive their clinical translation. This review offers valuable insights into the current state of research and highlights future directions for advancing innovative delivery systems.