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Theranostics 2020, Vol. 10, Issue 20 forms. Silver nanoparticles (AgNPs) have received special interest, especially in biomedicine. AgNPs are famous for their broad-spectrum and highly efficient antimicrobial and anticancer activities. Other biological activities of AgNPs have been also explored, including promoting bone healing and wound repair, enhancing the immunogenicity of vaccines [3], and anti-diabetic effects [4]. Deciphering the biological mechanisms and potential cytotoxicity of AgNPs will facilitate their better medical applications. Herein, we review the achievements of AgNPs in the past decade, especially focused on the past five years. This review intends to provide a valuable reference for researchers who are interested in the biomedical applications of AgNPs. The main contents include: • Synthesis of AgNPs, including physical, chemical and biological synthesis methods; • Medical applications of AgNPs, focusing on antimicrobial and anticancer properties and potential mechanisms, as well as other medical applications, including wound repair, bone healing, dental applications, vaccine adjuvant, antidiabetic agent, and biosensing; • The potential toxicity of AgNPs, including potential damages of AgNPs to many systems and organs in vivo, including skin, eyes, respiratory system, hepatobiliary system, central nervous system, urinary system, immune system and reproductive system. Numerous studies focus on the synthesis of AgNPs with controlled size and shape, and a variety of specific synthetic methods have been developed, including physical, chemical, and biological methods [5]. The predominant processes of the physical methods are classified into two parts: mechanical and vapor-based processes [6]. Conventional physical methods may involve mill, pyrolysis, and spark discharging [7]. Physical synthesis can obtain AgNPs with uniform size distribution and high purity [8]. Chemical synthesis is the most commonly used method to obtain AgNPs [8]. This method involves reducing silver ions to silver atoms [9], and the process can be divided into two steps, nucleation and growth [10]. Size- and shape-controlled AgNPs can be obtained by regulating the growth rate of nucleation. Besides reducing agents, capping agents and stabilizers also play important roles in obtaining AgNPs with good dispersion stability and uniform size distribution [11]. In addition, external energy can synergistically synthesize AgNPs, such as microwave, light, heat, and sound [12-15]. Although chemical synthesis methods of AgNPs are widely used, the 8997 toxicity and pollution caused by chemicals must be highlighted and more attention should be given. Compared with physical and chemical methods, the biological method proves an economical and environmental approach for AgNPs [8]. Micro- organisms include bacteria, fungi, and algae, as well as plant parts, include bark, peel, callus, leaves, flower, fruit, stem, seed, and rhizome are widely used in biological synthesis [16]. The organics, like enzymes, alkaloids, phenolic compounds and terpenoids, are abundant in extracts of microorganisms and plants, which can be available to reduce silver salts [16, 17]. Furthermore, some organic substances among these can also be used as stabilizers and capping agents [17]. Among the different methods, the additives mentioned may influence the subsequent medical applications of AgNPs. AgNPs are recognized for wide-spectrum and high antimicrobial activity, they can effectively kill a variety of pathogens even at very low concentrations [18], including (i) bacteria, such as Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus; (ii) fungi, such as Candida albicans, Aspergillus niger; (iii) virus, such as Hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Besides, some studies have shown that AgNPs have nematicidal and anthelmintic activity. The mainstream recognition of the antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure [18, 19]. Unlike the risk of antibiotic resistance which may limit medical applications, rare AgNPs resistance of bacteria is observed [20]. This may be attributed to the simultaneous multiple antibacterial mechanisms of AgNPs. In recent years, the anticancer effect of AgNPs has been widely studied. AgNPs play an efficient role against a variety of cancer both in vitro and in vivo, including cervical cancer, breast cancer, lung cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, hepatocellular carcinoma, glioblastoma, colorectal adenocarcinoma, and prostate carcinoma [21-23]. The anticancer activity of AgNPs is affected by inherent properties, including size, shape and surface charge [24-26]. Generally speaking, the smaller the particle size, the higher the biological activity. To obtain an ideal anticancer agent with high biological activity, our team successfully synthesized a kind of very small silver particles which reached up to Ångstrom (Å; one-tenth of a nanometer) scale and determined the stronger anticancer activities of silver Ångstrom particles (AgÅPs) compared with AgNPs [21]. In addition, exposure time and dose are also considered as crucial factors. Longer exposure time and higher dosage will trigger stronger anticancer effects. 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