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Theranostics 2020, Vol. 10, Issue 20 re-creating platforms. For example, Zeng et al. [306] synthesized hybrid Ag@NGO nanoparticles by a one-step reduction method. Among these platforms, the nanosized graphene oxide (NGO) worked as inert protective layers and provided an ultrathin protective layer for AgNPs. Ag@NGO exhibited the advantages of both SERS biosensing and drug delivery, ie, monitoring biomolecule signals in tumor cells through SERS biosensing and interacting with the anticancer drug doxorubicin through formation of π-π bonds. These results prove that AgNPs hold great application potential with capabilities of SERS biosensing. Silver nanoclusters have unique optical and electrical properties and can be used as materials for synthetic probes. While proteins have multiple chelating and functional groups, therefore, they have unique advantages as ligands in biological imaging. Cunlan Guo and Joseph Irudayaraj [307] used denatured bovine serum albumin as a stabilizer to synthesize silver clusters, which could sensitively and selectively detect the content of mercury. The probe had important application value for detecting mercury content in water, soil and food. Sun et al. [308] used glutathione as a ligand to passivate silver nanoclusters and obtained highly sensitive fluorescent probes. During the passivation of glutathione, the specific recognition of silver nanoclusters modulated from Hg2+ to Cu2+. This fluorescent probe was highly sensitive and selective in detecting Cu2+ in blood samples. The synthesis of silver nanoclusters with DNA as the backbone has excellent spectral and photophysical properties. The generation of this fluorophore is highly dependent on the DNA sequence. Oligonucleotide sequence changes may trigger the adjustment of the photo- luminescence emission band, thus identifying the mutant nucleotide sequence. Guo et al. [309] designed a double-stranded DNA scaffold that hybridizes probe DNA strands and sickle cell anemia mutation target DNA to generate fluorescent silver nanoclusters. The fluorescent silver nanoclusters specifically recognized sickle cell anemia mutations. The research extended from DNA scaffold single- stranded oligonucleotide to hybrid DNA double- stranded mutation site recognition, which may have more applications in the field of biological analysis. These studies suggest that silver nanoclusters have great clinical application potential. Potential Toxicity of AgNPs The potential harm of nanomaterials to organs and systems in the body has been gradually observed [310-312], which may influence the biomedical application of nanomaterial. Therefore, it is necessary 9016 to review the dynamics of AgNPs in vivo. AgNPs can be taken and distributed to different organs through a variety of routes of administration, mainly include inhalation, ingestion, skin contact, and subcutaneous or intravenous injection (Figure 5). The absorbed AgNPs are distributed in many systems [310, 311], such as the dermis, respiratory, spleen, digestive, urinary, nervous, immune and reproductive system, and mainly distributed in the spleen, liver, kidney and lung, while little deposition of AgNPs is observed in teeth and bones. The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier, and subsequently induce potential cytotoxicity . Besides the directly exposed tissues, AgNPs can also be transported to different organs via blood circulation. Therefore, the non-specific distribution of AgNPs may produce cytotoxicities such as dermal toxicity, ocular toxicity, respiratory toxicity, hepatobiliary toxicity, neurotoxicity and reproductive toxicity, which limit the applications of AgNPs. The potential cytotoxicity of AgNPs depends on the routes of administration and the properties or characteristics of the AgNPs, such as the size, shape, and concentration. At the cellular level, Wang et al. [313] used TEM and integrating synchrotron radiation- beam transmission X-ray microscopy (SR-TXM) with 3D tomographic imaging to capture the information of the cellular uptake, accumulation, degradation, chemical transformation, and removal of AgNPs. The experiment revealed that the cytotoxicity was caused by the chemical transformation of AgNPs, ie. Ag0 transformed into Ag+, Ag-O-, and Ag-S- species, which might induce the cellular biochemical changes. However, there is still inadequate acknowledge of the potential cytotoxicity , long-term adverse health effects, and the specific mechanisms of AgNPs accumulated in the different tissues and organs. In order to develop AgNPs with better biocompatibility for medical applications, it is urgent to systematically study their potential cytotoxicity. This chapter provides a brief overview of the potential toxicity and possible mechanisms of AgNPs in different organs, including skin, eye, kidney, respiratory system, hepatobiliary system, central nervous system, immune system and reproductive system (Table 6). Skin Toxicity Even as early as in 1614, Angelo Sala reported the first case of a definitive diagnosis of argyria, a kind of disease induced by the deposition of silver in tissues [314]. Since the mid-19th century, it has been recognized that silver or silver compounds may induce some tissues to turn gray or blue-grey, especially involving the skin. 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