Biomimetic Nanoparticle Drug Delivery Systems to Overcome Biological Barriers for Therapeutic Applications

Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.