Neutrophil‐Based Drug Delivery Systems

Abstract

White blood cells (WBCs) are a major component of immunity in response to pathogen invasion. Neutrophils are the most abundant WBCs in humans, playing a central role in acute inflammation induced by pathogens. Adhesion to vasculature and tissue infiltration of neutrophils are key processes in acute inflammation. Many inflammatory/autoimmune disorders and cancer therapies have been found to be involved in activation and tissue infiltration of neutrophils. A promising strategy to develop novel targeted drug delivery systems is the targeting and exploitation of activated neutrophils. Herein, a new drug delivery platform based on neutrophils is reviewed. There are two types of drug delivery systems: neutrophils as carriers and neutrophil-membrane-derived nanovesicles. It is discussed how nanoparticles hijack neutrophils in vivo to deliver therapeutics across blood vessel barriers and how neutrophil-membrane-derived nanovesicles target inflamed vasculature. Finally, the potential applications of neutrophil-based drug delivery systems in treating inflammation and cancers are presented.

Engineering Cell Membrane‐Based Nanotherapeutics to Target Inflammation

“…[71] These cells provide the initial barrier of the immune defense with its specialized granules. [71] These cells provide the initial barrier of the immune defense with its specialized granules.…”

“…[73] Extensive evidence has highlighted that neutrophils contribute to the pathogenesis of human inflammatory diseases such as sickle cell disease, chronic obstructive pulmonary disease, Behcet's disease, ischemic stroke, acute pancreatitis, and inflammatory arthritis. [71] Its targeting properties mainly depend on the phenotypic changes and surface molecules of neutrophils after leaving the bone marrow. [71] Its targeting properties mainly depend on the phenotypic changes and surface molecules of neutrophils after leaving the bone marrow.…”

Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

“…Furthermore, cell‐based delivery systems are intrinsically biodegradable, biocompatible, and non‐immunogenic. This “Trojan horse” approach has proved to be effective13 in delivering nanodrugs against cancer,14 inflammatory diseases,10,15 injury and infectious diseases 16…”

“…Cell-based drug delivery systems comprising of stem cells or immune cells are a promising alternative to synthetic particle carriers [8] since they naturally migrate toward injured tissues or tumors, and can show tissue/organ tropism based on specific surface markers. [9,10] Drugs can either be encapsulated inside or attached onto the surface of live cells, which protects them from premature degradation and thus ensures prolonged circulation, sustained release, and targeted delivery. [11,12] Furthermore, cellbased delivery systems are intrinsically biodegradable, biocompatible, and non-immunogenic.…”

“…[11,12] Furthermore, cellbased delivery systems are intrinsically biodegradable, biocompatible, and non-immunogenic. This "Trojan horse" approach has proved to be effective [13] in delivering nanodrugs against cancer, [14] inflammatory diseases, [10,15] injury and infectious diseases. [16] However, cell-based drug delivery systems are often difficult to image in real-time and do not release the encapsulated drugs out of the cells in a controlled manner, which limits their clinical application.…”