Preparation of diatom frustules incorporated with protein A-fused C-terminal silica-binding peptide and interpenetrating polymer network for targeted drug delivery.

Silica (SiO2), known for its high inertness, biocompatibility, and clearance, has become a promising material in drug delivery systems. However, the synthesis of fine-tuned mesoporous structure still faces challenges, such as complex procedures and the reliance on environmentally unfriendly chemicals; therefore, natural diatom frustules hold promise as an alternative silica material. In this study, protein A, an immunoglobulin G (IgG)-binding protein from Staphylococcus aureus, fused with a C-terminal silica-binding peptide (proA-C-Si-tag) was exploited as an adaptor protein to conjugate antibody to diatoms (Aulacoseira granulata) for targeted antibiotic delivery in bacterial treatment. The results indicated that the protein proA-C-Si-tag was successfully expressed in the soluble fraction by Escherichia coli BL21(DE3) and proA-C-Si-tag-bound diatoms displayed IgG antibody-capturing capacity. In addition, the diatom frustules were incorporated with poly-L-lysine and carboxymethyl cellulose to form an interpenetrating polymer network on the diatom via electrostatic interactions between these oppositely charged polymers for drug loading. The loading efficiency of thymolphthalein as a hydrophobic drug model was approximately 99% and the release rates at pH 7.4, pH 5.5, and pH 5 were about 7.3%, 9.4%, and 10.8% after 24 h, respectively. Finally, tetracycline-incorporated diatoms exhibited an antibacterial activity against methicillin-resistant Staphylococcus aureus. Collectively, this study was a groundwork for further diatom-based antibiotic delivery paradigms in antimicrobial applications.