Cargo-Compatible Encapsulation in Virus-Based Nanoparticles

Molecule encapsulation in virus-based nanoparticles (VNPs) is an emerging bioinspired way to design novel functional nanostructures and devices. Here, we report a general cargo-compatible approach to encapsulate guest materials based on the apparent critical assembly concentration (CAC_app) of VNPs. Different from the conventional buffer-exchange method, the new method drives the reassembly of VNPs to encapsulate cargoes by simply concentrating an adequately diluted mixture of VNP building blocks and cargoes to a concentration above the CAC_app. This method has been proved to work well on different types of cargoes (including inorganic nanoparticles and proteins) and VNPs. The major advantage of this method is that it can maximally preserve cargo stability and activity by providing the freedom to choose cargo-friendly buffer conditions throughout the encapsulation process. This method would benefit the realization of the potentials of VNPs and other protein nanocages as nanomaterials in diverse fields of nanotechnology.