INCORPORATION OF PROTEINS INTO EXPANDED-PORE MESOPOROUS SILICA

The development of oral vaccines faces challenges associated with the inactivation of antigenic proteins due to acidic pH and enzymatic degradation within the gastrointestinal tract. The use of ordered mesoporous silica has proven effective for the encapsulation, protection, and delivery of these antigenic proteins to the immune system. Considering its potential application to a wide range of proteins, silica pore size represents a limiting factor for the incorporation of these biomolecules. Here, the differences between conventional mesoporous silica (SBA-15) and an expanded-pore variant were investigated.

Comparative measurements demonstrated higher incorporation efficiency for globular proteins when using the expanded-pore variant. Furthermore, the integrity of the secondary structures of the proteins was evaluated before and after incorporation by Circular Dichroism (CD) and Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The obtained spectra demonstrated preservation of the native secondary structure elements, confirming that interaction with the inorganic matrix did not induce protein denaturation. Taken together, these results demonstrate that pore expansion in mesoporous silica enables the efficient incorporation and delivery of higher-molecular-weight biomolecules while maintaining their native conformation, which is essential for inducing a protective oral immune response.

The authors acknowledge the financial support from the National Institute of Science and Technology in Innovative Research in Health Sciences – from Nanotechnology to Artificial Intelligence (INCT PICS) sponsored by CNPq (grant 408417/2024-2), CAPES (grant 88887.197686/2025-00), and FAPESP (grant 2025/26818-7). FAPESP also sponsored the project via grants 2023/04532-9. This work was supported by grants #2026/07318-6 and #2022/01951-8 from the São Paulo Research Foundation (FAPESP), Brazil.