# Mini-Review: Potential of Diatom-Derived Silica for Biomedical Applications
## 5 Silica for Biomedical Applications: Advantages
### Surface Functionalization for Drug Loading and for Biosensing Clips for Biomedical Applications  
Frustule functionalization consists of modifying its surface to enable the formation of stable covalent bonds with proteins or DNA [26; 76], by introducing chemically reactive species functioning as cross-linkers. This step is crucial to improve the quality of the resulting material for specific applications. Chemical modification of biosilica can be critical, for example, to regulate the kinetics of drug release, and the high surface-to-volume ratio makes this raw material particularly suitable for drug delivery. Diatom frustules are characterized by precise and species-specific cell morphologies, and both the size and shape can highly differ among distinct diatom taxa. It has been estimated that the surface area ranges between 1.4 and 51 m\({}^{2}\) g\({}^{-1}\)[77; 78; 79; 80]. The size and the architecture of the pores are likely to influence drug release [75]. Drug release in biosilica-based systems is usually characterized by the following two phases: a first phase of fast release, due to the detachment of drug molecules weakly bound to the frustule surface, and a slow releasing phase, due to drug delivery from the internal pore structure of diatom frustules [81]. Chemical modifications of diatom-derived biosilica allow their use as a carrier of both soluble and insoluble drugs. The effectiveness of DEs as delivery systems for the drugs gentamicin (soluble) and indomethacin (insoluble) was demonstrated in previous studies [67], in which DE was modified with a self-assembling monolayer (SAM) including organosilanes and phosphonic acids, thus rendering the diatom frustules hydrophilic or hydrophobic, respectively, before drug loading. A sustained release of indomethacin, which has been exploited as a model drug for silica-based devices, was also demonstrated with DE particles functionalised by dopamine-modified iron oxide nanoparticles (DOPA/Fe\({}_{3}\)O\({}_{4}\) nanoparticles). Diatom-derived silica was employed, in this case, as a magnetically guided micro-carrier for drug delivery, since dopamine amino groups on the diatom surface allow the attachment of targeting biomolecules [78]. Another kind of functionalization can be obtained by combining the frustule with graphene oxide (GO) sheets through covalent bindings. These nano-hybrid composites are suitable drug microcarriers. GO sheets enhanced, indeed, drug-surface interactions, improving the kinetics of drug release [82]. Silica functionalization was also used to counteract cancer progression, through the delivery of water-insoluble antitumor drugs. A recent study showed that DE particles coated with vitamin B12 allowed better delivery of cisplatin and 5-fluorouracil (5-FU), two anticancer agents effective against colorectal cancer cells [83]. Silicon nanoparticles (SiNPs) were also functionalized with 5-FU and the chemopre eventing agent curcumin, and then encapsulated into acid-resistant microspheres to show the effectiveness of oral administration of these chemotherapeutics against colorectal cancer [84]. DE particles were also used as a solid drug-carrier in phospholipid suspensions for new oral formulations of non-anticancer water-insoluble drugs, such as the anticonvulsive carbamazepine [85]. While the abovementioned applications of biosilica were all based on the employment of fossil sources, other studies were focused on culture-derived biosilica. Functionalised frustules of the diatom _Nitzschia palea_ have been successfully exploited as carriers for the antibacterial complex tyrosine-Zn(II); zinc ions covalently bounded to the frustule surface showed, indeed, a toxic effect on bacteria, thus reducing their concentration [86]. [PERSON] et al. [87] exploited the potential of _Cheetceros_ sp. frustules to detect circulating tumour cells.