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Theranostics 2020, Vol. 10, Issue 20 silver salt precursor) to elemental silver (AgNPs) through electron transfer under certain conditions [8, 69]. In general, chemical synthesis can be promoted by reducing agents such as sodium borohydride (NaBH4) and sodium citrate (TSC). The chemical method can be combined with external energy sources to prepare AgNPs, such as photochemical, electrochemical, microwave-assisted and sono- chemical methods. Among these methods, the generation process of AgNPs can be divided into two parts: nucleation and growth. The monomer concentration in the solution rapid rises above the critical level of supersaturation, and triggers “burst-nucleation” and precipitation [70, 71]. The precipitation of the monomer forms the nucleus, and the repetitive nucleation process promotes the continuous birth of new seeds. As the seed formation, monomer concentration drops below the critical level of supersaturation. After nucleation, the increased addition of monomer induces the growth of nuclei and forms NPs with a larger size. During the synthesis process, stabilizers such as PVP and CTAB are usually used to stabilize and disperse AgNPs. Even though the chemical method of AgNPs is a reliable, high-yield, time-saving and controllable route, it must be noted that chemicals used in this method may cause environmental pollution. Chemical Reduction Method Chemical reduction is a reliable method for 9001 preparing colloidal AgNPs in organic solutions or water. AgNPs with desired shapes can be obtained by chemical reduction method, such as nanosphere, nanoprism, nanoplate, nanowire, nanocube, and nanorod. The chemical reduction method includes three components: salt precursor, reducing agent, and stabilizer. Silver precursors can be effectively reduced to AgNPs by different reducing agents with the presence of a stabilizer. There are several alternative silver precursors continuously providing monomers for nucleation, such as silver nitrate [69], silver ammonia ( ie. Tollens reagent) [72], silver sulfate [73], and silver chlorate [74]. Frequently used reducing agents may affect the growth of nuclei, including NaBH4, hydrazine, N, N-dimethylformamide, TSC, ascorbic acid, ethylene glycol, polysaccharides, and formaldehyde. The types and ratio of precursors and reducers, as well as the temperature and pH of the solution, may influence the characteristics of AgNPs [75-78]. The nucleation and subsequent growth of the particles in the chemical reduction process can be controlled by alternating the components and adjusting the reaction parameters. For example, Jiang et al. [78] studied the role of temperature in the synthesis of AgNPs by chemical reduction method (Figure 2). At the reaction temperature range of 0 to 55 °C, the low temperature significantly slowed down the generation of nuclei and growth, therefore, it took a longer time to complete the reduction of precursors. From 17 to 55 °C, the reaction rate increased with Figure 2. AgNPs synthesized at various temperatures. (A) The shape and size of AgNPs obtained in reaction systems at different temperatures ranged from 17 °C to 55 °C. (B) Transmission electron microscope (TEM) images of the AgNPs synthesized at different temperatures: (B1) 17 °C; (B2) 23 °C; (B3) 28 °C; (B4) 32 °C; (B5) 43 °C; (B6) 55 °C. (C) The average size of AgNPs (curve a: silver nanoplates; curve b: silver nanospheres) synthesized at different temperatures. Adapted with permission from [78], copyright 2011 Nanoscale Research Letters. http://www.thno.orgPDF Image | Silver nanoparticles Synthesis medical applications safety
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