Neutrophils, the most abundant leukocytes in the human body, have emerged as promising carriers for drug delivery due to their unique properties, including rapid response to inflammation, chemotaxis, and transmigration. When integrated with nanotechnology, neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles used in precise therapeutic interventions. These systems can coat nanoparticles with neutrophil membranes, load nanoparticles inside living cells, or engineer chimeric antigen receptor (CAR)-neutrophils. Neutrophil-inspired therapies show superior biocompatibility, targeting ability, and therapeutic robustness. This review summarizes the benefits of combining neutrophils and nanotechnology, the design principles and underlying mechanisms, and various applications in disease treatments. It also discusses the challenges and prospects for neutrophil-based drug delivery systems.
Neutrophil-mediated nano-drug delivery systems leverage the unique capabilities of neutrophils to enhance nanoparticle functionality and improve drug delivery efficacy. One strategy is to utilize neutrophil membrane for nanoparticle coating, creating a cell-mimicking formulation. Another approach directly utilizes neutrophils as carriers, allowing for precise and targeted drug delivery. Complementary to the role of neutrophils, nanotechnology leverages the responsiveness of nanomaterials, such as pH or GSH-responsive disassembly capability, to further enhance targeting precision. Technologies such as ultrasound and irradiation further contribute to the precise manipulation of carriers, facilitating controlled drug delivery. Genetic engineering techniques such as introducing CARs can also be applied to neutrophils in combination with nanotechnology.
Neutrophils are distributed in various organs and tissues, including the bone marrow, liver, lung, and spleen. In normal conditions, after intravenous administration, neutrophils have a relatively short half-life of approximately 7 h in the vascular compartment. Subsequently, they leave the circulation and home to the bone marrow and liver for destruction and clearance. In inflammatory conditions, neutrophils can target and migrate to the inflammatory sites owing to the mediation of chemotaxis. Chemokines orchestrate the entire process of neutrophil recruitment, from their release from the bone marrow to their directed migration.
Neutrophil membrane-encapsulated nanoparticles provide a shield that prevents the recognition and clearance by immune cells, allowing nanoparticles to remain intact and biologically active for enhanced efficacy. The transfer of surface markers, cell adhesion molecules, and receptors from neutrophil membrane to nanoparticles mediates the specific interaction with the target cells or tissues, facilitating targeted drug delivery. Various methods, including extrusion and ultrasonication, are used for neutrophil membrane coating. The size and shape of nanoparticles can influence their uptake by neutrophils, with larger particles (100–200 nm) being preferred. Neutrophils preferentially phagocytose particles with specific physical parameters, including size, shape, and surface roughness.
Whole neutrophils exhibitNeutrophils, the most abundant leukocytes in the human body, have emerged as promising carriers for drug delivery due to their unique properties, including rapid response to inflammation, chemotaxis, and transmigration. When integrated with nanotechnology, neutrophil-based nano-drug delivery systems have expanded the repertoire of nanoparticles used in precise therapeutic interventions. These systems can coat nanoparticles with neutrophil membranes, load nanoparticles inside living cells, or engineer chimeric antigen receptor (CAR)-neutrophils. Neutrophil-inspired therapies show superior biocompatibility, targeting ability, and therapeutic robustness. This review summarizes the benefits of combining neutrophils and nanotechnology, the design principles and underlying mechanisms, and various applications in disease treatments. It also discusses the challenges and prospects for neutrophil-based drug delivery systems.
Neutrophil-mediated nano-drug delivery systems leverage the unique capabilities of neutrophils to enhance nanoparticle functionality and improve drug delivery efficacy. One strategy is to utilize neutrophil membrane for nanoparticle coating, creating a cell-mimicking formulation. Another approach directly utilizes neutrophils as carriers, allowing for precise and targeted drug delivery. Complementary to the role of neutrophils, nanotechnology leverages the responsiveness of nanomaterials, such as pH or GSH-responsive disassembly capability, to further enhance targeting precision. Technologies such as ultrasound and irradiation further contribute to the precise manipulation of carriers, facilitating controlled drug delivery. Genetic engineering techniques such as introducing CARs can also be applied to neutrophils in combination with nanotechnology.
Neutrophils are distributed in various organs and tissues, including the bone marrow, liver, lung, and spleen. In normal conditions, after intravenous administration, neutrophils have a relatively short half-life of approximately 7 h in the vascular compartment. Subsequently, they leave the circulation and home to the bone marrow and liver for destruction and clearance. In inflammatory conditions, neutrophils can target and migrate to the inflammatory sites owing to the mediation of chemotaxis. Chemokines orchestrate the entire process of neutrophil recruitment, from their release from the bone marrow to their directed migration.
Neutrophil membrane-encapsulated nanoparticles provide a shield that prevents the recognition and clearance by immune cells, allowing nanoparticles to remain intact and biologically active for enhanced efficacy. The transfer of surface markers, cell adhesion molecules, and receptors from neutrophil membrane to nanoparticles mediates the specific interaction with the target cells or tissues, facilitating targeted drug delivery. Various methods, including extrusion and ultrasonication, are used for neutrophil membrane coating. The size and shape of nanoparticles can influence their uptake by neutrophils, with larger particles (100–200 nm) being preferred. Neutrophils preferentially phagocytose particles with specific physical parameters, including size, shape, and surface roughness.
Whole neutrophils exhibit