Smart materials in pharmacological drug development: Neutrophils and its constituents for drug delivery and consequent antitumor effects

Neutrophil-based drug delivery systems for targeted therapy of cancer have been studied widely in the recent past. Chemotactic cytokines including colony-stimulating factors (CSFs) recruit various immune cells including the neutrophils to the tumor microenvironment (TME) leading to enhanced metastasis. These cytokines can be targeted effectively by immunotherapeutic agents such as checkpoint inhibitors and mAbs that can lead to systemic toxicity. To minimize the systemic adverse effects, camouflaged nanoparticles can be used significantly as alternative therapeutic agents. The neutrophil-interacting NPs and neutrophil membrane coated NPs have been exploited recently for their antitumor properties in vitro and pose limited systemic adverse effects in vivo. Neutrophil-derived exosomes derived from immune cells can efficiently escape immune-surveillance and pass through the blood-brain barrier. They possess several intrinsic properties in drug delivery as they are nano-sized, extremely biocompatible, non-immunogenic, biodegradable, stable and can carry targeting agents with limited toxicity and display antitumor properties. Also, neutrophil-based nanotherapy is dependent on factors such as neutrophil kinetics and the physicochemical properties of NPs such as size, shape, and surface chemistry. Therefore, neutrophil-based drug delivery for cancer therapy via the use of polymer nanoparticles is widely studied as their clinical appliance in nanomedicine is still at its infancy.