Functionilzation Of Cell-derived Microvesicles Based On Bioorthogonal Click Conjugation

Cancer is a common disease which threatens the health and life of human being,but the treatment remains a great challenge in life science research.The existing treatments such as operation,chemotherapy and radiotherapy have poor effects with possible severe side effects.Thus,it is necessary and significant to explore a new type of cancer treatment.Microvesicles(MVs)are the membranous vesicles budded off from the plasma membrane.MVs are mediators for intercellular communication and material transportation,so it is a good choice to use MVs for drug delivery.Natural cell-derived MVs have the deficiency of poor targeting,so MVs should be functionalized before using for drug delivery.Based on the natural metabolic processes in cells,we develop a new method to functionally modify MVs.Firstly,we use AHA and PCho to culture cells to get AHA and PCho modified cells according to the protein and phospholipid synthesis pathway.Then,the donor cells are treated with starvation to obtain cell-derived MVs with propargyl and azide groups.Compared with the current methods for modifying MVs such as genetic engineering,our method is more simple,faster and of higher efficiency.What`s more,our method has less effect on the structure and function of MVs.Meanwhile,we acquire double labeled MVs which can trace and traget tumor at the same time by respectively connecting fluorescent molecule and modified antibody to MVs by copper-catalyzed click chemistry and free copper-catalyzed click chemistry reaction.We subsequently conduct a treatment experiment with the double labeled MVs and the result turns out to be satisfying.The present study provides a novel way to modify MVs,which could be used for biological research,tumor imaging and targeted drug delivery.