Design And Application Of Bioactive Nanomaterials Based On Cell Membrane

As the primary component of organisms,cells undertake various physiological functions.As the key barrier between cells and the surrounding environments,cell membranes are mainly composed of lipids,proteins,and carbohydrates.These substances are responsible for different functions,including recognition,adhesion,and substance exchange.Cell membranes have good biocompatibility,high safety,and easy access to modification.Due to these advantages,cell membranes have become a special kind of biomaterial.Numerous merits come from the combination of cell membranes bio-functions and nano-technology,reinforcing the important roles of cell membranes in the biomedical field.Here,three kinds of bioactive nanomaterials based on the different functions of cell membranes were designed for different applications.In Chapter 1,the composition and corresponding functions of cell membranes are introduced,in addition to the approaches regarding the extraction of cell membranes.Next,the construction methods of cell membrane-containing biomimetic nanomaterials are briefly summarized.Finally,the applications of nanomaterials based on the different functions of cell membranes in the biomedical field have been briefly reviewed.In Chapter 2,a cell membrane vaccine was established to prevent tumorigenesis.To solve the problem of low immunogenicity of tumor cell membranes as vaccine antigens,the expression of immunoreactive heat shock protein 70（HSP70）on the cell membrane was upregulated by radiation,and the metal manganese ions that can activate the innate immune response were combined to construct tumor prophylactic nanovaccines.HSP70 on tumor cell membranes promoted antigen presenting cells（APCs）to uptake and cross-presentation of cell membranes,causing stronger immune responses of T cells.Manganese ions could stimulate the activation of the macrophage c GAS-STING pathway,secrete type I interferon,and further activate T cells to produce antigen-specific immune responses.After vaccinations,the mice produced a strong specific immune response and long-term memory effect toward the same type of tumor cells.In Chapter 3,a new strategy was proposed for the control over stem cell differentiation.According to the interaction between environmental cells and stem cells in stem cell niches,we speculated that the coculture of cell membranes and stem cells can mimic cell-cell interactions and induce homologous directional differentiation of stem cells.Based on the differentiation lineage of mesenchymal stem cells,five different types of cell membranes were extracted and broken into nanometer size for more chances of the contact between cell membranes and stem cells.The ccell membranes were evidenced to induce homologic differentiation of mesenchymal stem cells,which finally expressed the same bio-markers of genes and proteins as the cell origin of cell membranes.The stem cells experienced the variations of cellular morphology like that of target cells.In additon,two mesenchymal stem cells from different sources showed identical results.These results indicating that cell membranes are potent to direct the differentiation of stem cells.In Chapter 4,biomimetic nanomaterials coated with tumor cell membranes were constructed with the capability of homologously targeting the tumor cells.The tumor cell membranes were exploited to encapsulate the amino-polystyrene nanospheres（PS-NH₂）that inhibit the m TOR pathway,which was loaded with the small molecule agonist GSK621 that activates the AMPK pathway.The nanomedicine was aimed to the disruption of the balance between the two energy-sensing pathways including AMPK and m TOR in tumor cells.After tumor cells took up the nanoparticles,the metabolization of the energy-related substances within upstream and downstream involved in the AMPK and m TOR pathways were disturbed.Subsequently,tumor cells were more vulnerable and sensitive to therapy approaches,such as the chemotherapy with doxorubicin（DOX）.