Functionalized Exosomes Reprogramming The Targeting Recognition Between Immune Cells And Tumor Cells

Exosomes are membrane-bound vesicles with a diameter of about 30～150 nm,generated by nearly all types of cells and widely distributed in various body fluids.As an important medium for material transport and communication between cells,exosomes directly affect various physiological states of cells and participate in the development of various diseases.As a non-invasive and cell-specific therapeutic nanocarrier,exosomes can effectively deliver cargo to target cells,reduce damage to normal cells,and enhance therapeutic efficacy.In this paper,natural exosomes were customized using genetic engineering and exogenous exosome isolation and modification techniques,preparing exosomes with specific biological functions and applying them to the targeted recognition effect of tumor cells and immune cells interaction,enhancing the capacity of immune cells to recognize tumor cells.To address the issues of low immunogenicity and off-targeting,fusion exosomes expressing vesicular stomatitis virus glycoprotein(VSVG)were obtained through endogenous modification,and functionalized exosomes reprogramming modified tumor cells were obtained using membrane surface modification techniques.The biological functions of the functionalized exosomes were verified,and their application potential in enhancing immune recognition was explored.The main research contents are as follows:1.Construction of fusogenic exosomes and membrane fusion effects.The biological properties of exosomes are inherently influenced by their parental cells and exhibit distinctive features and effects on their target cells.This paper used genetic engineering modification to transform parental cells to express the viral fusion protein with specific biological functions and secrete fusogenic exosomes(VSVG-Exos)surface-loaded with VSVG protein.Using mouse breast cancer cells as the subject of the study,a series of experiments were conducted to explore the membrane fusion effect between VSVG-Exos and mouse breast cancer cells.The results demonstrated that the VSVG protein was capable of regulating the interaction between VSVG-Exos and mouse breast cancer cells under acidic conditions,promoting membrane fusion between VSVG-Exos and tumor cell membrane surfaces.2.Functionalized exosomes reprogram the targeted recognition between tumor cells and immune cells.The interaction between tumor cells and immune cells is crucial for the success of cancer immunotherapy.Enhancing the mutual recognition effect between tumor cells and immune cells plays an important role in effectively eradicating tumor cells and inhibiting cancer development.In this paper,mouse breast cancer cells and dendritic cells were used as the research objects.By utilizing cell transfection and membrane surface modification techniques,natural exosomes were customized to produce functionalized exosomes that displayed viral fusion protein VSVG and DC-SIGN nucleic acid adaptors on their surfaces.The VSVG protein expressed on the membrane surface of functionalized exosomes could promote their membrane fusion with tumor cells under acidic conditions,transferring membrane surface information to tumor cells.Meanwhile,under the influence of DC-SIGN nucleic acid adaptors,immune cells were enabled to recognize and interact with tumor cells,thereby achieving enhanced precise recognition and specific targeting between the two cells.