Abstract

Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier in crossing immune systems and cellular membranes. To overcome these, various strategies have been explored including shuttling via liposomes or biocamouflaged nanoparticles. Here, we demonstrate the feasibility of loading antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell membranes, which can act as nanocarriers for intracellular delivery. Goat-antichicken antibodies are loaded into erythrocyte-derived nanovesicles, and their loading yields are characterized and compared with smaller dUTP-cargo molecules. Applying dual-color coincident fluorescence burst analyses, the loading yield of nanocarriers is rigorously profiled at the single-vesicle level, overcoming challenges due to size-heterogeneity and demonstrating a maximum antibody-loading yield of 38-41% at the optimal vesicle radius of 52 nm. The achieved average loading yields, amounting to 14% across the entire nanovesicle population, with more than two antibodies per loaded vesicle, are fully comparable to those obtained for the much smaller dUTP molecules loaded in the nanovesicles after additional exosome-spin-column purification. The results suggest a promising new avenue for therapeutic delivery of antibodies, potentially encompassing also intracellular targets and suitable for large-scale pharmacological applications, which relies on the exosome-mimetic properties, biocompatibility, and low-immunogenicity of bioengineered nanocarriers synthesized from human erythrocyte membranes.

Published in

ACS Omega
2024, Volume: 9, number: 21, pages: 22711–22718
Publisher: AMER CHEMICAL SOC

SLU Authors

• Ronquist, Göran

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

• Morrell, Jane

  • Department of Clinical Sciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Cell and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1021/acsomega.4c00650

Permanent link to this page (URI)

https://res.slu.se/id/publ/130212