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

Abstract

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-distearoylsn-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 (r 1 ) of BML is 3.71 mM −1 s −1 , which is comparable to the r 1 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.

Photothermal Properties of IR-780-Based Nanoparticles Depend on Nanocarrier Design: A Comparative Study on Synthetic Liposomes and Cell Membrane and Hybrid Biomimetic Vesicles

“…These results suggest that the membrane-protein content may be a limiting factor in the preparation of hybrid liposomes with a reduced mean size, at least for suspensions with a high particle concentration. In fact, Ferrel et al [ 7 ] fused erythrocyte membranes and synthetic liposomes to obtain a relatively narrow size distribution curve after 200 nm pore extrusion. However, they reported suspensions containing approximately 1 mg/mL lipids/erythrocyte membranes, while in this work, we used almost 10 mg/mL.…”

“…On the other hand, some well-known nanoparticles, such as synthetic lipid-based or iron oxide-based ones, are well established in the clinic, with several products on the market [ 1 ]. Synthetic nanoparticles can be produced on demand but might have enhanced performance if they are surface-modified, for example, by the hybridization of conventional liposome bilayers and cell membranes [ 5 , 6 , 7 ].…”

Indocyanine-type Infrared-820 Encapsulated Polymeric Nanoparticle-Assisted Photothermal Therapy of Cancer

“…PLGA with a carboxylic acid-terminated end group of molecular weight 50 kDa was used to synthesize IR-820 encapsulated PLGA nanoparticles following the well-established nanoprecipitation protocol. − In a typical experiment, the calculated amount of IR-820 in DMSO was physically adsorbed with 1 mg of PLGA in acetonitrile and made the final volume of the mixture to 1 mL to prepare IR-820-encapsulated PLGA nanoparticles. Then the phospholipids that consist of lipid mixture formulations having 260 μg of DSPE-PEG and 200 μg of DSPG were used in 4% ethanol, respectively.…”

A state-of-the-art liposome technology for glioblastoma treatment

“…RBC membrane-coated liposomes can enhance the loading, biocompatibility, and pharmacokinetics of drug molecules. 66,67 Therefore, RBC-based biomimetic drug delivery systems will be the next generation of drug delivery systems for brain tumor imaging and therapy. For example, in 2021, Fu, Shiyao et al designed and developed the dual-modified biomimetic nanoparticles using RBC-coated solid lipid nanoparticles (RBCSLN) and T7 and NGR peptide (T7/NGR-RBCSLNs).…”