Controlling the semi-permeability of protein nanocapsules influences the cellular response to macromolecular payloads

Nanocapsules are an excellent platform for the delivery of macromolecular payloads such as proteins, nucleic acids or polyprodrugs, since they can both protect the sensitive cargo and target its delivery to the desired site of action. However, the release of macromolecules from nanocapsules remains a challenge due to their restricted diffusion through the nanoshell compared to small molecule cargo. Here, we designed degradable protein nanocapsules with varying crosslinking densities of the nanoshell to control the release of model macromolecules. While the crosslinking did not influence the degradability of the capsules by natural proteases, it significantly affected the release profiles. Furthermore, the optimized protein nanocapsules were successfully used to deliver and effectively release a bioactive macromolecular vaccine adjuvant in vitro and, thus, can be used as an efficient platform for the design of potential nanovaccines.

Automated summary

Nanocapsules are a promising platform for delivering macromolecular payloads, but the challenge lies in controlling the release of these molecules. By varying the crosslinking density of the nanoshell, the release of model macromolecules from degradable protein nanocapsules can be controlled. These optimized protein nanocapsules have successfully delivered and released a bioactive macromolecular vaccine adjuvant in vitro, demonstrating their potential as efficient platforms for nanovaccine design.