# Nanostructured Biosilica of Diatoms: From Water World to Biomedical Applications  
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1 Department of Pharmacy, University of Naples Federico II, via [PERSON], 49, 80131 Napoli, Italy; [EMAIL_ADDRESS] (C.T. ); [EMAIL_ADDRESS] (M.T.) National Research Council, Institute of Applied Sciences and Intelligent Systems, Unit of Naples, 80131 Naples, Italy; [EMAIL_ADDRESS] (G.C. ); [EMAIL_ADDRESS] (I.R.) Correspondence: [EMAIL_ADDRESS]  
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centric diatoms, which show radial symmetry, and pennate ones, which are bilateral symmetric [7]. All motile diatoms are pennates, with two slits in each valve known as raphes. Diatoms are the principal organisms involved in the biosilicification, the process by which living organisms incorporate inorganic silicon in the form of silica [9]. In aqueous solution near the neutral pH, the main form of silicon is the orthosilicic (Si(OH)\({}_{4}\)). Beyond its solubility limit (2 mM), the orthosilicic acid turns into silica (SiO\({}_{2}\)) consisting of individual particles formed due to the repulsion between negatively charged particle surfaces [10; 11]. The orthosilicic acid is carried from the aquatic environment by specific silicic acid transporter proteins (SITs) and spilled into specialized vacuoles in the diatom, called silica deposition vesicles (SDVs). Within the SDVs, orthosilicic acid turns into hydrated amorphous silica thanks to the cooperation of long-chain polyamines (LCPAs), silaffin proteins, and polyanionic silacidin peptide. Long-chain polyamines modulate silica morphology by changing nanoparticles size, silaffin proteins stimulate silica formation, and the polyanionic silacidin peptide supports self-association of the positively charged molecules. The presence of different silaffins or different ratios of silaffins to LCPAs confers to each diatom species the unique morphology [12]. The variability of frustule morphology offers to scientists from various fields the possibility to choose the diatom species matching with the desired application. The species _Coscinodiscus_ has interesting radial symmetry with large and flat surfaces featuring well-organized multilevel pores [13]. Within this species, the diatom _Coscinodiscus granii_ has gained attention as slab waveguide photonic crystals thanks to the ordered periodic pattern of high and low refractive index [14]; the diatom _Coscinodiscus_ _wailesii_ has been widely studied due to the fact of its ability to focus light [15]. Diatom species with a nanoporous pattern, such as _Coscinodiscus concinus_, _Thalassioinsiru weissflogii_, _Thalassioira pseudonana_, and _Nitzschia_, have intrigued scientists for their capacity to deliver drugs, while other diatom species with nanometer-sized structures, such as _Odontella_ and _Phaeodactylum tricornutum_, are considered suitable for semiconductor nanolithography and photoluminescence spectroscopy [16; 17; 18; 19; 20]. Diatoms are an environmentally friendly source of silica and can be intensively cultivated in laboratories and photobioreactors on large scale [21; 22]. Figure 1: Scanning electron micrograph (SEM) of marine centric _Actinoptychus senarios_ (**a**) and pennate _Didymosphenia seminate_ (**b**) diatom frustules (skeletons). The image shows the typical structure of the frustules. The centric diatom (scale bar 10 \(\upmu\)m) shows a radial symmetry with circular valves, whereas the pennate diatom (scale bar 25 \(\upmu\)m) exhibits bilaterally symmetry. The pore pattern array (_areola_), the girdle bands between the valves, and the raphes are visible. Reproduced from Reference [8] with permission from The Royal Society of Chemistry. Diatoms have settled and fossilized on the ocean and freshwater floors over millions of years in the form of diatomaceous earth minerals [23; 24; 25; 26]. The amorphous silica surface shows high levels of free reactive hydroxyl groups (-OH) that can be exploited to modify the frustule with chemical groups (-NH\({}_{2}\), -COOH, -SH, and -CHO).