Drug delivery systems (DDSs) face significant challenges of unsatisfactory biocompatibility, biological barrier obstruction, immune clearance and suboptimal targeting efficiency, which greatly limit their clinical application. Natural endogenous materials have attracted widespread attention due to their high efficacy and biosafety. Among various natural materials, neutrophils (NEs), as the most abundant immune cells in the human body, exhibit intrinsic inflammatory chemotaxis, robust trans-barrier migration capacity, and high plasticity within the tumor microenvironment (TME), offering distinct advantages for the development of next-generation delivery systems. This review systematically summarizes the advances in drug delivery strategies for cancer treatment, with a focus on two principal approaches of NEs membranes modified therapeutic nanomaterials and whole NEs as “Trojan horse” carriers. The integrations of NEs-based DDSs with advanced therapeutic modalities, such as chemotherapy, phototherapy, immunotherapy and radiosensitization, have been thoroughly discussed for cancer treatments. Finally, the key challenges of NEs-based DDSs in clinical translation are highlighted, and the feasible solutions are also summarized to support the clinical applications of NEs-based delivery systems.
Chen et al. (Wed,) studied this question.