Cell as a factory for humanized encapsulation

摘要

Variety efforts are being made to develop colloidal based drug delivery systems (DDSs), which encapsulate cytotoxic drug in a vehicle and release them in a controlled manner. However, the synthetic carriers developed thus far are hampered by rapidly clearance in the body, for example by phagocytes, possibly due to the non-natural surface characteristics in terms of chemistry, morphology, and mechanics. To circumvent this important challenge, we have exploited living mammalian cells as factories to encapsulate drugs in "natural vesicles". These natural vesicles are termed cell membrane capsules (CMCs), because they maintain the major membrane structure and functions as well as cytosolic proteins of the parental cells. We demonstrate that CMCs act as unique delivery vehicles, in which encapsulated substances can be processed stepwise by cellular enzymes and then be selectively released through protein channels built-in the membrane, in a controlled and sustained manner. The preliminary study investigating the macrophage response to CMCs indicated the potential of CMCs to avoid attack by the immune system.