Oriented Assembly of Cell-Mimicking Nanoparticles via a Molecular Affinity Strategy for Targeted Drug Delivery

Abstract

Cell membrane cloaking is an emerging field in drug delivery in which specific functions of parent cells are conferred to newly formed biomimetic vehicles. A growing variety of delivery systems with diverse surface properties have been utilized for this strategy, but it is unclear whether the affinity of membrane−core pairs could guarantee effective and proper camouflaging. In this study, we propose a concise and effective "molecular affinity" strategy using the intracellular domain of transmembrane receptors as "grippers" during membrane coating. Red blood cell (RBC) membranes and cationic liposomes were adopted for fabrication, and a peptide ligand derived from the cytoplasmic protein P4.2 was prepared to specifically recognize the cytoplasmic domain of band 3, a key transmembrane receptor of erythrocytes. Once anchored onto the liposome surface, the P4.2-derived peptide would interact with the isolated RBC membrane, forming a "hidden peptide button", which ensures the right-side-out orientation. The membrane-coated liposomes exhibited an appropriate size distribution around 100 nm and high stability, with superior circulation durations compared with those of conventional PEGylated liposomes. Importantly, they possessed the ability to target Candida albicans by the interaction between the pathogenic fungus and host erythrocytes and to neutralize hemotoxin secreted by the pathogenic fungi. The curative effect of the model drug was thus substantially improved. In summary, the "molecular affinity" strategy may provide a powerful and universal approach for the construction of cell membrane-coated biomaterials and nanomedicines at both laboratory and industrial scales.

Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy

“…Meanwhile, the antibacterial effect was no better than vancomycin, which has faced serious problem of drug resistance. In summary, abundant studies have proved that RBCM-based nanoparticle systems are playing a promising role in delivering antibiotics [37]. However, there is still a lot of improvements to make, such as exploring dosage form of novel antibiotics, relatively simple preparation, safety and efficacy studies both in vitro and in vivo and so on.…”

Size Dependency of Circulation and Biodistribution of Biomimetic Nanoparticles: Red Blood Cell Membrane-Coated Nanoparticles

“…This inspires coating RBC membranes or other cell membranes to nanoparticles, camouflaging them in vivo and making them escape from the monitoring of the immune system. Studies have shown that RBC membranes with abundant self-markers can help the nanoparticles to escape from the recognition of the immune system, greatly extending the circulation half-life of poly(lactic-co-glycolic acid) (PLGA) nanoparticles from a few hours to approximately 40 h [7,8,9,10]. Our studies also demonstrated that RBC membrane-coated melanin, polypyrrole nanoparticles, or gold nanorods exhibited a longer blood circulation time and a higher tumor accumulation compared with bare melanin, polypyrrole nanoparticles, or gold nanorods [11,12,13].…”

Recent Advances of Cell Membrane‐Coated Nanomaterials for Biomedical Applications

“…A “molecular affinity” strategy was used to ensure the right‐side‐out orientation of RBC membrane on nanomaterials. [ 159 ] Cytoplasmic protein P4.2 would specifically recognize the intracellular domain of band 3, a transmembrane receptor of RBCs. Therefore, RBC membranes could coat on P4.2‐derived peptide‐anchored liposome with right‐out‐side orientation.…”