# Nanostructured Biosilica of Diatoms: From Water World to Biomedical Applications
## 3 Diatom Biosilica for Drug Delivery
This strategy was successful to control the release rate of both drugs and maintain a constant in situ molar ratio. DOX and PTX are often combined in therapy and require high molar ratio DOX/PTX to guarantee a synergistic effect. In this work, the siliceous core and the outer gel corona released a high amount of drug to the tumor site. The chemotherapeutic activity on Hela and HT1080 cancer cells was improved and,  
Figure 3: Schematic proof-of-concept of the self-assembled carrier for dual-delivery: the drug release from the core and corona of the functionalized diatom microparticles starts after the cleaving of matrix metalloproteinases-2 (MMP-2) specific peptides in the presence of MMP-2 enzyme. Reproduced from Reference [53], copyright (2020), with permission from Elsevier. as a consequence, the IC\({}_{50}\) value was lower than the free drug. Taking into consideration that the \(\beta\)-CD-capping lessens the release of encapsulated drugs from DEMP core, the shell structure was further optimized by incorporating a matrix metalloproteinases-2 (MMP-2) peptide as a linker between the core and \(\beta\)-CD: Ad shell. Since tumor-associated enzymes can degrade the linker, the strategy also resulted in a _stimuli_-responsive therapy. Both PTX and DOX showed enhanced and synergistic cytotoxic effects that outlined a valuable strategy for the encapsulation of different molar ratios of chemotherapeutics in diatom frustules. It is well known that the efficiency of a drug delivery system strongly depends on the strategy of encapsulation and the amount of drug in the carrier. Therefore, the improvement of drug encapsulation properties may lead to a stronger therapeutic approach and fewer side effects. Traditional techniques for drug encapsulation involve adsorption processes and electrostatic interactions between the drug and the outer carrier surface. In the last years, new strategies have been exploited to enhance the drug encapsulation efficiency of porous carriers. [PERSON] et al. (2016) developed an interesting silicon microfluidic device to encapsulate Isorhametin into in-house developed biogenic silica from _Cyclotella_ sp. frustules. The authors reported a loading capacity of 1.63%, which is an encouraging result for a novel methodology that reduces handling errors and time-consuming drug loading reactions. Frustules showed a typical release profile with an initial burst release of 48% of the drug in the first hour and the remaining in 3 h.  
Diatom biosilica has found application even in gene-therapy as nucleic-acid delivery systems ([PERSON] et al., 2016). [PERSON] et al. (2016) proposed engineered diatomite nanoparticles (DNPs) for short-interfering RNA (siRNA) delivery to lymphoma cancer cells. Diatomite nanoparticles were modified with amino-silanization and covalently conjugated to the Id-peptide (pA2036), a negatively charged peptide specifically recognized by B-cell receptors (BCR) on the A20 cell line. Poly-Arginine-small interference RNA was bound to DNPs through electrostatic interactions between siRNA positive charges and the negative surface of nanoparticles. Cells treated with the engineered DNPs-siRNA showed a decrease of \(40\%\pm 4.5\%\) of the targeted mRNA expressions, whereas only a 10% of decreasing expression occurred in cells treated with non-conveyed siRNA, resulting in a specific delivery of the siRNA only to target cells. [PERSON] et al. investigated the ability of modified DNPs to deliver siRNA to epidermoid cancer cells (H1355) as well ([PERSON]