ABSTRACT
Virus-like nanoparticles (VLPs) show considerable promise for the in vivo delivery of therapeutic compounds such as bioactive venom peptides. While loading and targeting protocols have been developed for numerous VLP prototypes, induced disassembly under physiological conditions of neutral pH, moderate temperature, and aqueous medium, remain a challenge. Here, we implement and evaluate a ring-opening metathesis polymerization (ROMP) general mechanism for controllable VLP disassembly that is independent of cell-specific factors or the manipulation environmental conditions such as pH and temperature that cannot be readily controlled in vivo. The ROMP substrate norbornene is covalently conjugated to surface-exposed lysine residues of a P22 bacteriophage-derived VLP, and ROMP is induced by treatment of water-soluble ruthenium catalyst AquaMet. Disruption of the P22 shell and release of a GFP reporter is confirmed via native agarose electrophoresis and quantitative microscopy and light scattering analyses. Our ROMP disassembly strategy does not depend on the particular structure or morphology of the P22 nanocontainer and is adaptable to other VLP prototypes for the potential delivery of venom peptides for pharmacological applications.
Competing Interest Statement
The authors have declared no competing interest.
ABBREVIATIONS
- VLP
- Virus-Like Particle
- ROMP
- Ring-Opening Metathesis Polymerization
- P22
- Bacteriophage P22
- CP
- P22 coat protein
- SP
- P22 scaffold protein
- GFP
- green fluorescent protein
- BBB
- blood-brain barrier
- DLS
- dynamic light scattering
- TEM
- transmission electron microscopy
- PDI
- polydispersity index