The Preparation Of Paclitaxel-globin Nanoparticles And Its Targeting Effect On Macrophages Highly Expressing CD163

The tumor microenvironment is a hypoxic, low pH, high interstitial pressure, rich in growth factors and proteolytic enzymes local steady-state system, which provides the necessary material basis for the occurrence, development, invasion and metastasis of tumor. In a manner of speaking, the tumor microenvironment can be said to be the soil of tumor. In addition to the tumor cells, there are a large number of non-tumor cells and extracellular matrix in the tumor microenvironment. The focus on tumor therapy has been transferred from the tumor cells to the entire tumor microenvironment, people are trying to change the tumor microenvironment so as to achieve the effect of suppressing tumor.The tumor-associated macrophages (TAM), a group of macrophages resident in the tumor tissue, are the major components of the non-tumor cells in the tumor microenvironment. More and more evidences verify the truth that TAM plays an important role in the occurrence, growth, invasion and metastasis of tumor. TAM is mainly characterized by M2phenotype in tumor development, so it’s generally be classified as M2macrophages. M2macrophages highly express IL-10and receptors such as CD163, CD204and CD163. TAM is weak in antigen-presenting, with a higher ability of debris removal, it can promote tumor development by supporting angiogenesis, tissue remodeling, wound repair and suppression of the immune response. The theory that TAM is a potential target for tumor treatment has been confirmed by the researches that the inhibition of TAM can inhibit tumor.CD163is exclusively expressed on the surface of monocytes (low expression) and tissue macrophages (high expression) such as TAM. The main function of CD163is to mediate the internalization of hemoglobin-haptoglobin complexes (Hb-Hp) by macrophages. In addition, CD163can also mediate endocytosis of hemoglobin (Hb) and chemical modified Hb derivatives in the absence of haptoglobin (Hp) by macrophages. Nanoscale drug carrier systems targeting CD163can be specifically directed to TAM in the purpose of suppressing tumor by inhibiting TAM. The traditional method is to modify the surface of the nanoscale drug carrier systems with Hb or CD163monoclonal antibody, so that the nanodrugs can actively target CD163. In the present study, we have prepared a special kind of paclitaxel-globin nanoparticles. As the carrier material of prepared nanoparticles, globin derived from Hb has a potential of actively targeting CD163. After carrying out a detailed characterization of nanoparticles, we investigated its ability of targeting CD163in vitro. The experiment results confirm that nanoparticles are able to target CD163highly expressing macrophages indeed in vitro. In addition, we also proved that paclitaxel-globin nanoparticles have the potential of inhibiting tumor by inhibition of the TAM in the tumor cell chemotaxis experiments.