Virus‐Mimicking Cell Membrane‐Coated Nanoparticles for Cytosolic Delivery of mRNA

Abstract

Effective endosomal escape after cellular uptake represents a major challenge in the field of nanodelivery, as the majority of drug payloads must localize to subcellular compartments other than the endosomes in order to exert activity. In nature, viruses can readily deliver their genetic material to the cytosol of host cells by triggering membrane fusion after endocytosis. For the influenza A virus, the hemagglutinin (HA) protein found on its surface fuses the viral envelope with the surrounding membrane at endosomal pH values. Biomimetic nanoparticles capable of endosomal escape were fabricated using a membrane coating derived from cells engineered to express HA on their surface. When evaluated in vitro, these virus-mimicking nanoparticles were able to deliver an mRNA payload to the cytosolic compartment of target cells, resulting in the successful expression of the encoded protein. When the mRNA-loaded nanoparticles were administered in vivo, protein expression levels were significantly increased in both local and systemic delivery scenarios. We therefore conclude that utilizing genetic engineering approaches to express viral fusion proteins on the surface of cell membrane-coated nanoparticles is a viable strategy for modulating the intracellular localization of encapsulated cargoes.

The Future of Tissue-Targeted Lipid Nanoparticle-Mediated Nucleic Acid Delivery

“…Targeting ligands can also be engineered directly into the coating membrane. Park et al, for example, coated an mRNA polyplex with a mouse melanoma membrane engineered to express a viral fusion protein that enhances endosomal escape, dramatically improving transfection efficiency both in vitro and in vivo [ 78 ]. A more general targeting approach than cancer cell membrane homotypic targeting and active targeting are utilizing platelet membrane coatings, which have been shown to target a variety of disease states, including vascular disease, infections and cancer [ 75 ].…”

Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

“…These complexes expressed fusion protein hemagglutinin and mimicked the virus's capability of endosomal escape, which was exploited to attain mRNA delivery through IN administration. [192] Similarly, the macrophage membrane could be modified on the surface of PLGA NPs forming functionalized NPs that were capable of eliciting the potent immunity against Pseudomonas aeruginosa when delivered via IN. [193] Angsantikul et al also utilized the bacterial membrane coated gold NPs to effectively remedy the antibiotic-resistant bacterial infection via IN route.…”

Membrane-fusogenic biomimetic particles: a new bioengineering tool learned from nature

“…Recently, Park et al designed an HA-displayed cell membrane-coated nanoparticle for the membrane-fusion-mediated cytosolic delivery of mRNA. 18 This nanoparticle was formulated by coating an HA-expressed cell membrane on the poly(lactic- co -glycolic acid) (PLGA) cores carrying mRNA. Through HA-mediated membrane fusion with tumor cells in the acidic environment, these developed virus-mimicking particles successfully transfected model mRNA payloads (EGFP and Cypridina luciferase) both in vitro and in vivo .…”