# Nanostructured Biosilica of Diatoms: From Water World to Biomedical Applications
## 2 Chemical Modification of the Frustule Surface
The resulting biodegradable and biocompatible DOX-loaded AF (Chi@AF-DOX) exhibited discernible hemolytic effects compared to free DOX, which, instead, is known to cause many side effects including cardiotoxicity. This study offers an interesting reflection on the ability of polymer-functionalized drug carriers to reduce the toxicity of the chemotherapeutic drug and outlines their promising applications for cancer therapy. [PERSON] et al. [41] were the first to outline the great potentiality of diatoms for drug delivery and many efforts have been done to investigate and improve diatom frustule applications to date. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, but their production often involves costly and toxic chemicals. [PERSON] et al. proposed a cost-effective porous drug carrier represented by polydopamine (PDA)-coated diatom frustules modified with folic acid (FA) ligands for controlled and _stimuli_-responsive curcumin (CUR) release [42]. In this study, purified frustules loaded with curcumin (DE-CUR) were coated with PDA, which acted as a gatekeeper by controlling the curcumin release and simplified the conjugation of the ligand FA on the surface of diatoms (DE-CUR-PDA). The release of curcumin from the modified carrier was slightly slower than the unmodified one (DE-CUR), thanks to the interactions between the thin PDA layer and the drug, which delayed its release from the carrier. The drug release was more rapidly when the medium pH decreased from 7.4 to 1.2, due to the rupture and disassembly of PDA coating. Since abnormal pH has been universally recognized as a diagnostic hallmark of cancer, pH-responsive carriers that can change their chemical or physical properties are promising candidates for cancer treatments [43]. The challenging treatment of cancer is mainly attributed to its multifactorial nature. In the past decades, the alteration of redox balance has been illustrated as one of the most important factors underlying tumor development, its progression and invasion into neighboring tissues. Oxidative stress can damage cells, proteins, and DNA, playing a considerable role not only in neoplastic disease but also in diabetes, cancer, and neurodegenerative pathologies [44]. In some cases, reactive oxygen species (ROS) production can be induced by drug intermediates generated during metabolism and can increase drug toxicity. Chemically modified diatom frustules with both drug delivery and scavenger properties were investigated by [PERSON] et al. to reduce the drug-induced oxidative stress caused by Ciprofloxacin (CPFX) administration [16]. To this aim, nanostructured biosilica produced by _Thalassiora weissflogii_ frustules was covalently bound via a silanization strategy to the cyclic nitroxide 2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) in consideration of its ability to scavenge superoxide, peroxide, and alkyl radicals. Alongside this, the antimicrobial drug CPFX was encapsulated into diatom frustules. The intention was to deliver the CPFX to cells and simultaneously decrease the drug-induced oxidative. The authors confirmed the efficacy of the silanization strategy for covalent attachment of molecules on the surface of diatom frustules and outlined the therapeutic potential of this material to reduce oxidative stress. The ability of carriers to reduce the drug release rate and control drug diffusion to cells is a critical point that can be addressed by engineering the surface of the carriers. The porous ultrastructure of the frustule can be coated with polymers preventing the burst release of the therapeutic molecule. These coated frustule elements can then find applications in site-specific delivery of drugs. Recently, drug selectivity and targeted drug delivery have been reported to decrease undesirable side effects to healthy cells and reduce patient suffering. [PERSON] et al.