# Nanostructured Biosilica of Diatoms: From Water World to Biomedical Applications
## 3 Diatom Biosilica for Drug Delivery  
Targeted carriers offer the opportunity to improve the selective accumulation of active agents in diseased tissue and cells. By adding targeting agents to drug carriers, we could control the destination of the drug and increase the likelihood of response. To deliver chemotherapeutic drugs to CD20\({}^{+}\) B-cells specifically, [PERSON] et al. [17] realized a nanoporous biosilica platform from naturally engineered microalgae. The diatom _Thalassisisisis pseudonana_ was genetically modified via recombinant DNA technology: a synthetic sequence that encodes the IgG-binding domain of protein G (GB1) was fused to the amino-terminal peptides S and T8, which are naturally expressed on the frustules. The GB1-biosilica was further labeled with Rituximabab, an antibody specific for the CD20 molecule expressed on B-cells. The specificity of the antibody-labeled-frustules was demonstrated by in vitro and in vivo studies. Antibody-labeled frustules bound to B-lymphocytes release the drug more efficiently than untargeted ones. Indeed, 54% of B-cells interacted with modified-frustules, whereas none of the T-cells exhibited interactions with unmodified-frustules. Positively charged lipid-based colloids loaded with camptothecin (CPT) and 7-ethyl-10-hydroxy-CPT (SN38) were electrostatically adsorbed on the surface of modified microalgae. The dual-step strategy for drug encapsulation provided effective CPT and SN38 loading efficienic is 61.2% and 85.8%, respectively. Cytotoxicity tests assessed on SH-SYSY neuroblastoma and baby hamster fibroblast (BSR) cell lines confirmed the possible application of genetically modified frustules for targeted cancer therapy (for in vivo research, see the dedicated Section 6). [PERSON] et al. have recently functionalized diatom frustules belonging to the genera _Aulacoseira gramulata_ with vitamin B\({}_{12}\) for Cisplatin and 5-fluorouracil (5-FU) delivery to colorectal cancer cells [48]. Colorectal cancer was selected as a disease model since it is one of the most recurrent tumors in humans, and its pathogenesis strongly correlates with diet and lifestyle factors [49]. The B\({}_{12}\) functionalization strategy was based on the idea that cancer cells need more vitamin B\({}_{12}\) and show a higher expression of the transcobalamin II receptor (TCII) on the surface. Vitamin-B\({}_{12}\)-modified frustules (DEMs-B\({}_{12}\)) provided a high drug concentration at the site of action while minimizing off-target exposure. Cisplatin and 5-FU were encapsulated into DEMs-B\({}_{12}\), by Vasani method [50] with a loading efficiency of 5.9% and 9.9%, respectively. Frustule drug encapsulation is a suitable strategy to deliver different drugs, but the burst release of the drug in aqueous media (generally within 1 h) hinders drug delivery applications of frustules. In this study, 90% of the drug was released from modified frustules within 4 h. Hence, carrier functionalization can positively affect the carrier release properties and offer suitable prospects for controlled therapy. Combined therapy is the cornerstone of all cancer treatments and, in most cases, the cause of therapy failure due to multidrug resistance (MDR) phenomena [51; 52]. [PERSON] et al. [53] employed self-assembled microparticles obtained from diatomaceous earth (DEMP) for the dual delivery of chemotherapeutic agents. They overcame the antagonist effect between the drugs by using a different molar ratio of chemotherapeutics. (Figure 3). The self-assembled platform was obtained by tethering diatom microparticles to the homodifunctionalized-linker 1-adamantylamine (Ad-DEMPs) as a guest molecule to get a host-guest interaction with \(\beta\)-cyclodextrintrin (\(\beta\)-CD) (Figure 3). Doxorubicin (DOX) and paclitaxel (PTX) were encapsulated in two different compartments: the siliceous core and the self-assembled \(\beta\)-CD with ad-thixotropic gel corona on the surface of microparticles, respectively.