Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans ; Drug Delivery Systems/methods* ; Neutrophils ; Phagocytosis ; Drug Carriers ; Blood-Brain Barrier ; Neoplasms/drug therapy*

Objective To study the effect of bifidobacterium on intestinal tissue of necrotizing enterocolitis (NEC)in newborn rats and its regulation of Wnt/β-Catenin signal pathway.Methods Seventy -five newborn SD rats were randomly divided into 5 groups,and each group had 1 5 rats.Group A was artificial feeding control group;group B was NEC model group;group C was bifidobacterium treatment group;group D was artificial feeding +bifidobacterium control group;group E was rat breast feeding control group.The localization expression of Toll -like re-ceptor 4(TLR4)of ileocecal ileum tissue was detected by immunohistochemical detection,and also the equivalen-tileum tissues were detected for the contents of glycogen synthase kinase -3β(GSK3β)and β-Catenin expression by Wes-tern blot.Comparing the differences of these indicators between the groups,in addition,the data of TLR4,GSK3βandβ-Catenin were analyzed by Bivariate correlations.Results The levels of TLR4 in ileum tissue of 5 groups were 0.36 ±0.03,0.48 ±0.05,0.34 ±0.03,0.37 ±0.04,0.35 ±0.02.The levels of GSK3βin ileum tissue of 5 groups were 0.98 ±0.23,1 .48 ±0.42,0.99 ±0.20,0.56 ±0.1 7,0.60 ±0.1 5.The levels of β-Catenin in ileum tissue of 5 groups were 1 .48 ±0.22,0.64 ±0.55,1 .27 ±0.36,1 .72 ±0.51 ,1 .82 ±0.44.The levels of TLR4 and GSK3βin ileum tissue of group B were significantly increased compared with group E (P <0.05).The levels of β-Catenin sig-nificantly decreased compared with group E (P <0.05).The levels of TLR4 and GSK3βin ileum tissue of group C were significantly decreased compared with group B (P <0.05).The levels of β-Catenin significantly increased com-pared with group B (P <0.05).Negative correlation was observed between the levels of GSK3βand β-Catenin(r =-0.592,P <0.05),while positive correlation was observed between the levels of TLR4 and GSK3β(r =0.295,P <0.05),and negative correlation was observed between the levels of TLR4 and β-Catenin(r =-0.426,P <0.05). Conclusions Bifidobacterium has certain protective effect on the NEC newborn rat intestines,which can reduce the in-cidence of experimental NEC and the severity of intestinal injury.Its effect may be achieved by regulating the Wnt/β-Catenin signal pathway,which decreases the expression of the level of GSK3βand increases the level of repair fac-tor β-Catenin.

Objective To investigate the effects of lipopolysaccharides (LPS) in different concentrations on the proliferation and interleukin(IL)-6,IL-1 β and tumor necrosis factor-α(TNF-o) secretion of intestinal epithelial cells (IEC-6) of rats in vitro.Methods IEC-6 of rats were divided into normal group (0 mg/L,group A),0.1 mg/L group (group B),0.5 mg/L group (group C),1.0 mg/L group (group D),5.0 mg/L group (group E) and 10.0 mg/L group(group F).Different groups cells were exposed to LPS with different concentrations for 3 h,5 h and 7 h.Thiazolyl blue(MTT) was performed to investigate the proliferation of IEC-6.The concentrations of IL-6,IL-1 β and TNF-α in culture supernatant were detected by enzyme linked immunosorbent assay(ELISA).Results The proliferation rate of IEC-6 was gradually lower while the concentration of LPS increased.After co-culture with LPS 3h and 5 h,the proliferation rates of group B,group C,group D,group E and group F had no significant difference with those of group A (all P ＞ 0.05);after co-culture with LPS 7 h,the proliferation rates of group B,group C,and group D had no significant difference with those of group A (all P ＞ 0.05);the proliferation rates of group E and group F had significant difference with those of group A(t =4.216,P =0.014;t =14.991,P =0.000).The proliferation rates of group E and group F were lower after co-culture with LPS 5 h than 7 h,and there were significant differences (t =2.576,P =0.033;t =2.975,P =0.018);but there was no significant differences between group E and group A after co-culture with LPS 5 h (P ＞ 0.05).Group B,group C,group D,group E and group F all had a significant higher level of IL-6 than group A after co-culture with LPS 3 h,5 h and 7 h(all P ＜0.01).In addition,group E had the highest level of IL-6 at all time points.And the peak level of IL-6 rose after co-culture with LPS 5 h.The TNF-α level and IL-1 β level of group B,group C,group D,group E and group F all had no significant differences than that of group A after co-culture with LPS 3 h,5 h and 7 h (all P ＞ 0.05).Conclusions In a certain concentration,incubation time range,the proliferation rates of IEC-6 cells were gradually lower while the concentration of LPS increased.Co-cultured IEC-6 cells with LPS(0-10.0 mg/L) can stimulate them secrete to IL-6.The highest level of IL-6 was of group E after 5 h co-culture.LPS had no effects on TNF-α and IL-1 β level of IEC-6 cells cultural supernatant.So 5.0 mg/L concentration of LPS stimulating IEC-6 cells for 5 h can be chosen to build the IEC-6 inflammatory models.