Proteins from the solid-binding peptide family can be adapted to a wide range of nanoparticles. The foundational design concept of Silinker can be applied not only to nanosilica but also to other nanocarriers.

During the functional validation of CS, TS, PS, and NS, SBP's binding to silica presented challenges as many instruments involved glass components, rendering many existing experimental setups unusable. In future work, we need to explore alternative experimental approaches that avoid the use of silica. Additionally, due to insufficient time to express proteins suitable for validating Silinker's functionality (e.g., GFP and YFP for FRET experiments), we were unable to test certain concepts related to Silinker's regulation of protein distance and relative positioning. We hope to validate and test our Silinker using a wider range of functional proteins in future work.

Up to this point, we have only expressed Silinker in a prokaryotic system. Although this system is simple to operate and cost-effective, it lacks post-translational modifications, and proteins tend to form inclusion bodies. In future work, we plan to express CS, TS, PS, and NS proteins in a eukaryotic expression system to obtain Silinker protein more effectively.

Due to difficulties in large-scale preparation, we were unable to test the concept of using nucleic acid aptamers and nucleic acid switches instead of peptides as structural domains for response signals in NS proteins. In future experiments, we hope to use nucleic acid aptamers to replace peptide segments, achieving further modularization and orthogonality for Silinker.

Due to various reasons, we did not obtain mesoporous silica nanoparticles (MSN), which prevented us from testing the interaction between Silinker and the surface pores of MSN, as well as the impact of this interaction on drug loading. In future work, we hope to acquire MSN and investigate the interaction between our Silinker and the surface pores of MSN to assess its effects.

In our initial concept, we aimed to enable different Silinkers to cooperate and form an "electronic circuit" on the surface of silica, allowing for mutual regulation and interaction. Due to the current limitations in our work, we have not been able to fully test and fine-tune each Silinker, so there is still a significant distance to go before realizing this design. However, we believe that as we gradually fine-tune the Silinkers, we can ultimately construct signal-responsive and regulatory pathways on silica carriers, transforming nano-silica into an intelligent platform.