posted on 2021-04-21, 15:06authored byMikail
D. Levasseur, Shiksha Mantri, Takahiro Hayashi, Maria Reichenbach, Svenja Hehn, Ying Waeckerle-Men, Pål Johansen, Donald Hilvert
Nanoparticle-based
delivery systems have shown great promise for
theranostics and bioimaging on the laboratory scale due to favorable
pharmacokinetics and biodistribution. In this study, we examine the
utility of a cage-forming variant of the protein lumazine synthase,
which was previously designed and evolved to encapsulate biomacromolecular
cargo. Linking antibody-binding domains to the exterior of the cage
enabled binding of targeting immunoglobulins and cell-specific uptake
of encapsulated cargo. Protein nanocages displaying antibody-binding
domains appear to be less immunogenic than their unmodified counterparts,
but they also recruit serum antibodies that can mask the efficacy
of the targeting antibody. Our study highlights the strengths and
limitations of a common targeting strategy for practical nanoparticle-based
delivery applications.