# Sol-Gel Silica Nanoparticles in Medicine: A Natural Choice. Design, Synthesis and Products
## Silica Biogeochemical Cycle
This highly reactive biogenic silica deposit layer resulted from the silica-based skeletal remains of tiny aquatic organisms (diatomaceous and silicified phytoplankton) deposited over millions of years, and may include minor amounts of quartz, oxides of Ca, Mg, Fe and Al, and even some organic matter, depending on their location (Figure 2). More importantly, silica performs an essential role in many, if not all, forms of life [38]. The weathering and deterioration of rocks allows for high silica contend in soils (from \(<\)1 to 45% dry weight [52]) in the form of soluble [Si(OH)\({}_{4}\)] or Si(OH)\({}_{3}\)O\({}^{-}\) species (with concentrations ranging from 0.1 to 0.6 mM [53]), allowing its uptake by plants, thus entering the food chain [54; 55]. Although not traditionally thought of as an essential element in plants' life cycles, Si is found in plants at concentrations varying from 0\(\cdot\)1 to 10% (\(\sim\)10\({}^{3}\)-10\({}^{5}\) mg kg\({}^{-1}\), dry weight basis), an amount equivalent to, or even exceeding, several macronutrients [53]. Biogenic silica occurs in many single-cell organisms, as natural amorphous structures with the composition SiO\({}_{n}\)(OH)\({}_{4-2n}\). The skeleta of diatoms (_Diatomene_, 5 um up to 60 um) are formed with silica. Upper plants like _Equisetaceae_ may accumulate 1 up to 10% silica (in dry weight), _poaceae_, _Equisetaceae_ and _Cyperaceae_ families have silica values \(>\)4% wt, the _Cucurbitales_, _Uriticales_ and _Comelinaceae_ families accumulate an intermediate Si content (2-4% wt Si), while most other species contain trace amounts of silica. Nevertheless, silica is known to favor the healthy growth, development and reproduction of plants, increase their resistance to fungi, enhance their mechanical resistance, apart from not being detrimental when excessively collected [56] (Figure 3). Figure 3: Leaf blast symptoms in rice after inoculated with _Magnaporthe grisea_ for 10 days. Rice plants were continuously treated with (+Si) or without silicon (\(-\)Si) (**A**). Silica layer was formed in the cell wall of Si-treated plants and enhanced plant resistance to fungi infection by physical barriers (**B**). Reprint with permission from [57]. Figure 2: The diatomite deposition in the Mediterranean region. Reprint with permission from [51]. In the human body, silica's effects in health, aging and disease are still being explored, notwithstanding its average content of ca. 260 ppm, very close to the magnesium level (accounting for 18 g in a person with 70 kg) [58; 59]. Silica is pivotal in calcium phosphate nucleation, determinant in bone mineralization, growth and self-healing during dislocations and fractures [59]. Aluminum absorption and (eventual) intoxication in human body (particularly important in [PERSON]'s disease) may be prevented by silica ingestion, through the bonding to Al in the gastrointestinal tract [60; 61]. Maintenance of health in the immune system and reduction of the risk of atherosclerosis are other of silica attributes [62]. Silica also accounts for the maintenance of tissue integrity by stabilizing the glycoproteins associated with collagen, thus playing a central role in the structural integrity of nails, hair, and skin [63]. Amorphous silica could enter in the human body via the gastro-intestinal tract (in colloidal form) and has been part of human dietary either as medical clay, or as food additive (labelled E551) [64; 65]. Contrary to crystalline silica, associated with lungs cancer and silicosis [66; 67], a-SiO\({}_{2}\) NPs seem essentially nontoxic [68]. Any (eventual) inflammation process associated with a-SiO\({}_{2}\) NPs is dependent on the NP size, shape and synthesis methodology, being no unambiguous linking of physical-chemical properties of a-SiO\({}_{2}\) and human toxicity, bioavailability, yet possible [68; 69; 70; 71; 72; 73; 74; 75; 76].