Re-engineering a Liposome with Membranes of Red Blood Cells for Drug Delivery and Diagnostic Applications

Red blood cells (RBCs) make up the overwhelming majority of cells in the vascular system, spending most of their lives wandering the vast network of vessels that permeate every tissue of our bodies. Therefore, the delivery of any class of therapeutic agent that must stay in the circulatory system may benefit from being carried by RBCs. Toward this direction, we have re-engineered a synthetic liposome with the membranes of RBCs and incorporated a magnetic resonance imaging (MRI) contrast agent gadolinium along with the chemotherapeutic drug doxorubicin (DOX) to form a biomimetic liposome (BML). The BMLs proposed herein consist of biocompatible/biodegradable synthetic phospholipids, which include 1,2-distearoyl-sn-glycero-3-phosphoglycerol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and gadolinium-conjugated lipids. These synthetic phospholipids have been fused with a natural RBC membrane and are loaded with DOX using the extrusion technique. BMLs were characterized for their physicochemical properties, stability, fusogenic (between synthetic and natural lipid from RBC), magnetic, drug loading, biocompatibility, and cytotoxicity properties. BMLs had a hydrodynamic diameter of 180 ± 20 nm with a negative surface charge of 29 ± 2 mV. The longitudinal relaxivity (r₁) of BML is 3.71 mM^-1 s^-1, which is comparable to the r₁ of commercial contrast agent, Magnevist. In addition, DOX-loaded BML showed a cytotoxicity pattern similar to that of free DOX. These results showed the potential of using the proposed BML system for both MRI-based diagnostic applications and drug delivery platforms.