# Protein Nanocages as Building Blocks for Conjugated Supramolecular Materials Displaying Multitasking Properties

## TL;DR

Scientists used virus-like particles decorated with different proteins to create multitasking biomaterials with potential for vaccines and drug delivery.

## Contribution

A new method for conjugating different virus-like particles using SpyTag-SpyCatcher to create multitasking biomaterials.

## Key findings

- VLPs decorated with different proteins were successfully conjugated using SpyTag-SpyCatcher technology.
- The resulting conjugates retained the individual properties of each component.
- This approach enables the creation of novel multitasking biomaterials.

## Abstract

Protein nanocages are a group of compartments naturally enclosing nucleic acids or proteins for biological purposes. Such materials have also inspired the design of novel proteins displaying self-assembling properties. The most studied protein nanocages are viral capsids and their derivative virus-like particles (VLPs), which consist of any or all of the structural proteins of the virion but lack nucleic acids and are therefore non-infectious. VLPs can be used as vaccine antigens or decorated with heterologous antigens to develop new vaccine materials. External surfaces of VLPs can also be decorated with chemical substances to impart new properties, like fluorescence tags or binding to cellular receptors. In addition, the internal space of VLPs can be used to encapsulate therapeutic materials that can be carried to specific cells or tissues. Although VLPs are naturally polyvalent and can display more than one decorating element, it is possible to expand the repertoire of decorating species by specifically conjugating different VLPs, which can be decorated with different functional elements. Here, VLPs of parvovirus B19 displaying different functional proteins were linked through the SpyTag-SpyCatcher biorthogonal conjugation technology. Characterizing the resulting species demonstrated the bioconjugation and the presence of the individual properties of each component. This proof-of-concept research implies that novel multitasking biomaterials can be constructed from protein nanocages and that the application landscape is vast and highly expandable.

The online version contains supplementary material available at 10.1007/s12010-025-05364-4.