The Construction And Preliminary Application Of Biomimetic Drug Carrier Based On Cell Membrane Vesicles

Bionic drug carrier can provide an effective way for the treatment of diseases.Cell derived extracellular vesicles(e.g.,exosomes,microbubbles)have good biocompatibility and low immunogenicity,and have been used in tumor therapy,toxin clearance and other research and achieved good therapeutic effect.However,these vesicles from natural sources have some problems,such as low production and complicated separation and purification,which limit their application.In view of the above problems,our research group has developed a new method for the preparation of cell membrane vesicles(MVs),which can efficiently and rapidly prepare MVs with excellent properties in the culture medium,laying a research foundation for the biological application of cell membrane vesicles.Based on these previous studies,we explored the feasibility of cell membrane vesicles as drug carriers and regulated the structure of cell membrane vesicles in order to expand their biological applications,the details are as follows:In the second chapter,we used MVs to load curcumin,a small hydrophobic drug,to investigate the therapeutic effect of MVs as a drug carrier on tumor cells.Curcumin can be effectively loaded into MVs by simple co incubation.The loading capacity and stability of curcumin were investigated by using the fluorescence characteristics of curcumin.Through cytotoxicity test,we found that compared with curcumin alone,the killing effect of curcumin loaded MVs on tumor cells was significantly improved,and it also showed better therapeutic effect on multi drug resistant tumor cells.We further investigated the therapeutic effect of MVs loaded with different anti-tumor drugs and using MVs from different cell sources as biomimetic drug carriers.The results showed that MVs from different sources could effectively carry drugs for anti-tumor treatment.In addition,different anti-tumor drugs loaded into the cell membrane vesicles can effectively improve the therapeutic effect of drugs,indicating that the use of cell membrane vesicles to carry drugs in the treatment of tumor has good universality.We discussed the interaction mechanism between MVs and tumor cells as drug carriers.The preliminary results showed that MVs may deliver drugs to tumor cells by membrane fusion and play a role.In the third chapter,DNA nanotechnology was used to assemble and regulate the structure of nano cell membrane vesicles(nano-MVs).By squeezing the vesicles,we obtained uniform sized vesicles,and then designed DNA triangular prism with A and B different arm chains.Through the connection of p H sensitive linker chains,we realized the assembly and disassembly of nano-MVs.Furthermore,we designed and constructed different sizes and structures of Nanovesicles by molecular self-assembly method,which provides a new method for multifunctional tumor therapy based on cell membrane vesicles.