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Cell-Specific Delivery Using an Engineered Protein Nanocage
Mikail D Levasseur1, Shiksha Mantri1, Takahiro Hayashi1
1Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
ACS Chemical Biology
|April 21, 2021
Summary
Protein nanocages offer potential for targeted drug delivery and bioimaging. However, while antibody binding enhances cell uptake, it can also attract interfering antibodies, limiting therapeutic efficacy.
Area of Science:
- Biotechnology
- Nanomedicine
- Protein Engineering
Background:
- Nanoparticle delivery systems show promise for theranostics and bioimaging.
- Protein-based nanocages can be engineered for biomacromolecular cargo encapsulation.
Purpose of the Study:
- To evaluate a protein nanocage system for targeted delivery of encapsulated cargo.
- To investigate the impact of antibody-binding domains on nanocage immunogenicity and targeting efficacy.
Main Methods:
- Engineered a cage-forming variant of lumazine synthase to encapsulate cargo.
- Linked antibody-binding domains to the nanocage exterior for targeted cell uptake.
- Assessed nanocage immunogenicity and the effect of serum antibodies on targeting.
Main Results:
- Antibody-binding domains facilitated cell-specific uptake of encapsulated cargo.
- Protein nanocages showed reduced immunogenicity compared to unmodified versions.
- Recruitment of serum antibodies by the nanocages partially masked targeting antibody efficacy.
Conclusions:
- Protein-based nanocages are a viable platform for targeted delivery applications.
- The presence of serum antibodies presents a challenge for antibody-mediated targeting strategies.
- Further optimization is needed to overcome limitations for practical nanoparticle-based delivery.
