CHEMICAL SCIENCE

Neutrophil-based bone marrow-targeted drug delivery system


On April 20, 2023, Beijing time, Professor You Jian’s team of Zhejiang University published a new paper titled “Neutrophil hitchhiking for drug delivery to the bone marrow” in the journal Nature Nanotechnology.

This study reports a bone marrow-targeted drug delivery system based on neutrophils at specific life stages, which uses the characteristics of senescent neutrophils to return to bone marrow apoptosis to efficiently deliver free or nanodrugs into the bone marrow, providing the possibility for early diagnosis and treatment of bone-related diseases.

The corresponding authors of the paper are You Jian, Luo Lihua and Li Qingpo, and the first author is Luo Zhenyu.

Bone-related diseases such as bone tumors in situ or bone metastases, osteomyelitis, osteoporosis, and osteoarthritis are clinically common. Although with the rapid development of medicine in recent decades, corresponding therapeutic drugs have been developed for various bone-related diseases, but due to the existence of the blood-bone marrow barrier and the low blood perfusion of bone, the content of drugs entering the bone marrow is still low, resulting in poor treatment effect of some bone-related diseases, or the need for larger doses to meet basic treatment requirements.

Bone marrow-derived neutrophils are among the most common cells in the body. Neutrophils mature in the bone marrow and migrate into the bloodstream. At this time, neutrophils express high CXCR2 and low expression CXCR4, and after being stimulated by inflammatory signals (such as IL8), they will be recruited to the inflammatory site to kill invading pathogenic microorganisms. However, the half-life of neutrophils is only a dozen hours, and most of the neutrophils gradually move towards aging during blood circulation, during which the expression of CXCR2, which was originally highly expressed, is down-regulated, and the expression of CXCR4 is upregulated, and finally stimulated by the chemokine CXCL12 secreted by bone marrow stromal cells, re-migrates back to the bone marrow through the CXCR4/CXCL12 axis and apoptosis.

Based on this, the team of Professor You Jian of Zhejiang University proposed to develop a neutrophil-based bone marrow-targeted drug delivery system using the fate of neutrophils in vivo. After ingesting free drugs and drug-loaded nanoparticles by neutrophils with bone marrow tendencies, their ability to target bone marrow was demonstrated by PET/CT and IVIS. Next, the team applied the drug delivery system to two different disease models: in the breast cancer bone metastasis model, the use of neutrophil delivery of cabazitaxel significantly inhibited tumor growth; In the osteoporosis model, the use of neutrophils to deliver teriparatide can significantly increase bone density and reduce osteoporosis related indicators.

Figure 1: Schematic diagram of a neutrophil-based bone marrow-targeted drug delivery system.

Figure 2: In vivo biodistribution of neutrophil-delivered free drugs or nanoparticles.

Figure 3: Therapeutic effect on breast cancer bone metastases and osteoporosis.

In summary, this study reports a neutrophil-based bone marrow-targeted drug delivery system, that is, using the characteristics of senescent neutrophils returning to bone marrow apoptosis, free drugs or drug-loaded nanoparticles are efficiently delivered to the bone marrow, improving the therapeutic effect of bone-related diseases such as bone metastases and osteoporosis. (Source: Science Network)

Related paper information:https://doi.org/10.1038/s41565-023-01374-7



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