# Sol-Gel Silica Nanoparticles in Medicine: A Natural Choice. Design, Synthesis and Products
## 1 Introduction  
Silica (SiO\({}_{2}\)) has been used throughout history in the manufacturing of glass, ceramics, concrete, mortar, sandstone and silicones [1]. Today, silica is present in an impressive variety of everyday life products, such as glass and tableware, vitroceramics, domestic and industrial water membranes, plastics, paper, paints, silicones, semiconductors, fiber and optical glasses, electronic, optoelectronic, aerospace, and defense products [2; 3; 4], to mention some of them. As regards healthcare and medicine, SiO\({}_{2}\) is a current material in dentistry (tooth implants, ceramic pastes) [5; 6], orthopedics (bone implants, scaffolds) [7; 8], dermatology [9] and specialized medical devices (ophthalmological and bio-glasses, scaffolds) [10; 11; 12; 13]. The coming of nanomedicine opened the door to new engineered materials/devices opportunities, colloidal silica having pride of place among micro and nanoparticles (NPs) [14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24]. Nanomedicine initiated a new attitude towards conventional medicine, where challenges are addressed using a _bottom-up_ rather than _top-down_ approach, medical actions are performed at a single cell level, tailor made therapeutic prescription are performed, _theranosis_ (where diagnosis and therapeutic meet) is designed [25]. _Nanomedicine_ is based on _nanocarriers_ (nanosystems, nanoplatforms, NPs) capable of simultaneous targeting, sensing, signaling, and drug releasing distinct drugs/markers, with different pharmacokinetics/pharmacodynamics, to elaborate optimized _tailor-made_ treatments/diagnosis. Cell tracking (in regenerative medicine or in the early detection of cancer) is carried out across all major imaging modalities--like magnetic resonance imaging (MRI), magnetic particle imaging (MPI),computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT), to ultrasound (US), and optical (fluorescent) imaging [26] and journals like _Cancer Imaging_ and _Cancer Imaging and Diagnosis_. Spatial and temporal controlled drug delivery (throughout injectable or oral nanocarriers) redesigned disease treatment ([27; 28; 29; 30; 31; 32] and _Advanced Drug Delivery Reviews_). While introducing thousands of times less drug into the body nanomedicine scaled down the possibility of side effects, like tissue or organ inflammation or destruction, and at the same time increased the localization of pharmaceutical drugs in the diseased tissue. Moreover, engineered NPs maybe fine-tuned relatively to thermal, electrochemical, catalytic, electronic and magnetic properties or designed to respond to micro-environmental (pH sensitivity, enzyme sensitivity) or external (magnetic field, light) triggers [33; 34; 35; 36; 37]. As a nanocarrier, silica competes with biological materials (like phospholipids, lipids, lactic acid, sugars, proteins such as dextran or chitosan, virus), synthetic polymers (carbon or silicon-based), and other inorganic materials (ceramics, metals) (Table 1, Figure 1). Silica's high thermal stability, chemical inertia (at PTN conditions), microbial attack immunity, along with strong surface energy, high hydrophilicity and biocompatibility, impermeability (or weak permeability), great chemical versatility (due to the possibility of in situ/ex situ physical functionalization, through second order chemical bonding, or chemical functionalization, in highly specific conditions), high loading capacity for drugs/chemicals/therapeutic molecules associated with ease of processing [38; 39] are the properties that made it so special, a cost-effective, hard to beat material. Furthermore, amorphous silica and silicates are generally recognized as safe by the U.S. Food and Drug Administration [40], to be used as oral delivery ingredients in amounts up to 1500 mg per day, and have been widely applied as an additive in cosmetics, food, and oral drugs [41; 42]. Figure 1: Engineered multifunctional NP.