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Theranostics 2020, Vol. 10, Issue 20 follicle cells. Conclusion and prospect Over decades, AgNPs have been studied rapidly and extensively due to the unique physical, chemical, optical, electronic and catalytic properties. These properties are closely related to characteristics of AgNPs, especially the size and shape. AgNPs with different characteristics can be produced by physical, chemical and biological routes. External energy sources such as light, heat, electricity, sound and microwave can be used in the synthesis process. Various factors should be considered in the synthesis of AgNPs with expected size and shape. Besides the types of precursor salts, additives such as reducing agents,cappingagentsandstabilizers,aswellasthe importance of reaction parameters, including reaction temperature, time, pH and extra energy sources should be recognized in the production process. Among these methods, biological synthesis using bacteria, fungi and plant extract proves a simple, environmentally friendly, cost-effective and reliable approach. Compared with physical and chemical methods, biological method does not require high temperature or toxic/hazardous additives, but the potential pathogens need to be carefully considered. We review the synthesis methods of AgNPs and compare the advantages and disadvantages to help understand how to obtain nanoparticles with controlled size and shape. AgNPs have broad prospects in medical applications. Among them, antimicrobial and anticancer properties have received more attention. A variety of factors influence the antimicrobial and anticancer effects of AgNPs, including size, concentration/dose, exposure time, stabilizer and surface charges. The proposed mechanisms for antimicrobial activity of AgNPs involve destroying the structure of cell wall, inducing ROS production and DNA damage. Anticancer mechanisms of AgNPs are more complicated. AgNPs can induce apoptosis and necrosis of cancer cells by destroying cell ultrastructure, inducing ROS production and DNA damage, inactivating proteins and regulating multiple signaling pathways. Besides, AgNPs may block invasion and migration of cancer cells by inhibiting angiogenesis within the lesion. However, the potential cytotoxicity of AgNPs may limit their medical applications. In order to improve the compatibility of AgNPs, proper surface functionalization is widely concerned. The AgNPs surface allows coordination of multiple ligands and thus can be functionalized. The surface functionalization of AgNPs can simultaneously improve their biological safety and challenge their 9024 drug delivery, which is conducive to the development of more antibacterial and antitumor agents involving AgNPs. AgNPs can also be used as an additive or adjuvant in bone scaffolds, dental materials and vaccines. The antidiabetic effect of AgNPs is also explored. Besides the impressive antimicrobial and anticancer activities, the unique optical properties of AgNPs make them great clinical potential in the field of biosensing and imaging. The AgNPs surface allows coordination of multiple ligands and thus can be functionalized. Although most studies focus on the therapeutic purposes of AgNPs, the potential toxicities of AgNPs in multiple systems including skin, eyes, kidney, respiratory system, hepatobiliary system, immune and reproductive systems have been discussed. Further in-depth studies are required to evaluate the biocompatibility and potential cytotoxicity of AgNPs, which may help to develop safer and biocompatible AgNPs-based agents. In this review, we separately introduce the synthesis method and anticancer properties of Ång- scale silver particles in the relevant sections. Compared with AgNPs mentioned in this review, we prepared pure and fine silver particles with Ångstrom size. This ultra-fine size may be a threshold for silver particles in the medical applications, that is, Ång-scale silver particles exhibit broad-spectrum anticancer activities without obvious cytotoxicity . This exciting discovery inspires us to explore more promising applications of Ång-scale silver particles in nanomedicine. Acknowledgments This work was supported by the Special Funding for the Construction of Innovative Provinces in Hunan (Grant Nos. 2019SK2301, 2020SK3002), the National Natural Science Foundation of China (Grant Nos. 81670807, 81871822), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No. 2019-RC-HL-024), the Science and Technology Plan Project of Hunan Province (Grant Nos. 2017XK2039, 2018RS3029) and the Innovation Driven Project of Central South University (Grant Nos. 2019CX014, 2018CX029). Author Contributions H.X. guided the planning and writing of the review manuscript. L.X., H.X. and Y.-Y.W. wrote the manuscript. L.X. and J.H. prepared the figures. H.X., C.-Y. C., Z.-X.W., L.X. and Y.-Y.W. amended the manuscript. Competing Interests The authors have declared that no competing http://www.thno.orgPDF Image | Silver nanoparticles Synthesis medical applications safety
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