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.

Regulation of Synovial Macrophages Polarization by Mimicking Efferocytosis for Therapy of Osteoarthritis

“…Over the last decade, cell membrane‐coated NPs have been extensively studied. [ 17a,18 ] To construct cell membrane encapsulated NPs, the apoptotic membrane was mixed with MOFs‐Que NPs and the suspension was formed in an ultrasonic bath. We also constructed normally cultured chondrocytes membrane encapsulated NPs as a control.…”

“…Preparation of apM@MOFs-Que: apM@MOFs-Que and chM@ MOFs-Que were prepared using the method described by Zhang et al. [18] Typically, MOF-Que was well dispersed in ultrapure water at a concentration of 1 mg mL. −1 Next, apM suspension was added to the yellow suspension at a core to membrane protein weight ratio of 1:1 and immediately sonicated using a bath sonicator (42 kHz, 100 W) for 4 min to form the membrane-coated NPs.…”

Formulation of Lipid-Free Polymeric Mesoscale Nanoparticles Encapsulating mRNA

“…Modification of the mesoscale nanoparticle formulation to incorporate the high molecular weight hydrophilic mRNA molecule [ 34 , 35 ]. To evaluate the optimal and most facile formulation method, we modulated the volume in which the mRNA was added in the primary mixture, proceeded to the nanoprecipitation step, and measured MNP size, charge, and PDI to ensure they retained the optimal mesoscale nanoparticle physicochemical characteristics [ 23 , 24 ].…”

An Integrated Polymeric mRNA Vaccine without Inflammation Side Effects for Cellular Immunity Mediated Cancer Therapy

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Recently, mRNA-based vaccines have emerged as a promising strategy for the prevention and treatment of infectious diseases and cancers, benefiting from the inherent advantages of mRNA (i.e., facile manufacture, inherent immunogenicity, and low insertional mutagenesis risk). [14][15][16][17][18][19][20][21] mRNA vaccines against infectious diseases have been extraordinarily successful for clinical use and in which the protection against infection is mainly endowed by strong humoral immunity. By contrast, therapeutic mRNA vaccines against cancer must also induce a robust Among the few available mRNA delivery vehicles, lipid nanoparticles (LNPs) are the most clinically advanced but they require cumbersome four components and suffer from inflammation-related side effects that should be minimized for safety.…”

“…[ 1–13 ] Recently, mRNA‐based vaccines have emerged as a promising strategy for the prevention and treatment of infectious diseases and cancers, benefiting from the inherent advantages of mRNA (i.e., facile manufacture, inherent immunogenicity, and low insertional mutagenesis risk). [ 14–21 ] mRNA vaccines against infectious diseases have been extraordinarily successful for clinical use and in which the protection against infection is mainly endowed by strong humoral immunity. By contrast, therapeutic mRNA vaccines against cancer must also induce a robust cytotoxic CD8 + T cell mediated cellular immunity to eradicate cancer cells.…”