**3.6 Wound healing activity**

*Applications of Nanobiotechnology*

**3.4 Diagnostic agent**

**3.5 Catalytic agent**

of biosensors. For instance, electrochemical biosensor is performed by fixing the potential at a suitable value and determining the current changes versus time. The role of NPs in this type of biosensor is to improve sensitivity and signal detection [59]. In optical biosensors, the free electron oscillation in conduction bands of some metals (Ag, Au, Cu) interacts with light photons and produces a polariton. Size tuning of plasmonic metals is a way for enhancing surface plasmon resonance and making the device suitable for biomedical applications. Using NPs leads to reaching to highest detection sensitivity. Au NPs because of their easy functionalization and showing different colors based on their size and shape are good choices for colorimetric biosensor, plasmonic sensing, immune sensors, and electrochemistry [60]. The Au NPs showed unique stability compared to other metals when used for bio-conjugation production and have valuable sensitive plasmon change which lead to their wide use in classic immunoassays. The stronger Raman and fluorescence enhancement of Ag NPs than Au NPs resulted to their broad uses in optical applications [61]. Also they can easily be oxidized and be used in electrochemical sensors. Ag NPs with ability to detect proteins have been used for cancer detection. Furthermore they were also used for detecting glucose, DNA, dopamine, ascorbic acid, and several other biological molecules. Magnetic NPs are used in sensors through three main approaches including pre-concentration of analyte, magnetic

The special features of NPs such as fluorescence properties, optical scattering and electromagnetic field enhancement, and even transferring light energy to heat resulted in a wide application of these compounds in medical diagnostic field. Furthermore, NPs are excellent carriers for delivery of active biomedical agents. Biomedical imaging is one of the useful tools for human disease diagnosis. The NPs with special optical, magnetic, and radioactive properties can enhance the quality of imaging. It is possible to functionalize NPs with multiple modals and by this way minimize the interface between each modality and provide multimodal agent for better imaging [64]. The optical nano-probes can be designed for being used in linear optical imaging with high-emission quantum energy yield and expanded optical capacity. In the case of fluorescent imaging, the degradation of organic dyes (photo bleaching) and metal complexes under light exposure is alleviated with fluorophore-doped silica NPS. These NPs have been used for untargeted imaging of human epithelial cells of the cervix and targeted imaging of cells A549, HeLa, and HepG2 [65, 66]. Phosphorescence imaging using NPs produced images with lower background autofluorescence and scattered excitation light in the spectral range. Magnetic resonance imaging (MRI) used contrast agents for detection of small tumor and lesions in a normal tissue. The NPs with magnetic functionality are used

in MRI, and the ones with larger magnetic moment are preferred [67].

NPs have been developed for various catalytic applications. The NP catalytic reactions have several advantages including low reaction temperature, light transparency, and easily immobilization on solid supports, for instance, the catalytic activity of Au NPs in degrading methylene blue demonstrated by Khan et al. [68]. Also the effect of geometrical parameters of supported Au NPs on its carbon monoxide oxidation has been evaluated. The NPs with an average diameter of 2 nm and height of six atomic monolayers showed optimum catalytic activity [69]. The Au NPs on amorphous silica support produced by Mukherjee et al. were able

tags, and integration into transducer materials [62, 63].

**8**

NPs are a suitable wound dressing agent because of their valuable antibacterial, anti-inflammatory effects and ability to accelerate skin reepithelialization. Reports of healing effects of Ag NPs indicated that these nanoscale materials decrease local matrix metalloproteinase and neutrophil apoptosis. Also they showed inhibitory effects on pro-inflammatory cytokines interferon gamma and tumor necrosis factor alpha [72]. The combination of Ag NPs and collagen results in the formation of component with suitable antibacterial activity. Au NPs do not have any antibacterial effects alone, but their combination with biological agents like collagen and gelatin improve their biocompatibility and biodegradability and make them suitable for wound dressing. Au NP antibacterial properties resulted from their interaction with cell membrane and inhibiting ATP synthase which consequently lead to ROS-independent cell death. The reports indicated that the combination of Au NPs, gallate, and epigallocatechin has positive effects in healing of mouse skin wounds through regulation of angiogenesis and anti-inflammatory effects [73]. Pd, Pt, Se, and ZnO are other promising NPs for regenerative medicine and wound healing. The PAPLAL® solution (Toyokose Pharmaceuticals, Japan) (Shibuya et al. 2014) which is a mixture of Pd NPs and Pt NPs showed protective effects against agingrelated skin pathologies and normalized the gene expression levels of Mmp2, Has2, TNF-α, and IL-6 in the skin [74].

Zn NPs have valuable antibacterial effects, and its topical application leads to reduction of inflammation and improvement of skin reepithelialization. TiO2 NP wound treatment enhances body fluid coagulation by making interaction with blood proteins. The formation of adherent crust of a nanocomposite improved healing of wound and inhibited infection and inflammation [75].

Also nanotechnology can be used for delivery of active agents with antimicrobial, anti-inflammatory, and healing effects. Curcumin treatment of diabetic wounds leads to significant enhancement in reepithelialization and an increase in fibroblast proliferation of injured tissue. Curcumin NPs not only have higher lifetime than curcumin but also showed valuable antibacterial effects against methicillin-resistant *Staphylococcus aureus* [76]. With respect to molecular chemistry and self-assembly approaches, it is possible to develop peptide NPs with a variety of medical applications.

Polymeric NPs using both biological and synthetic polymers are of great interest for the development of wound dressing compound. Polymeric NPs are able to stimulate cell proliferation through enhancing angiogenesis and reepithelialization. They are able to stimulate the infiltration of inflammatory cells in the initial phase of healing. Furthermore, they are suitable carriers for therapeutic agents including cytokines, growth factors, and antibiotics which make them suitable for being used in treatment of both normal and delayed infectious wounds [77, 78].
