Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles

*Paritosh Patel, Puja Kumari, Suresh K. Verma and M. Anwar Mallick*

#### **Abstract**

Toxicity and biocompatibility of silver nanoparticles are of a major concern due to their extensive production regardless of their application in current industries. Information about toxicology or biocompatibility is crucial regarding their proper utilization and application in clinical as well as environmental aspect. This chapter describes in detail about the different techniques and technology of synthesis of silver nanoparticles and explains their different physiochemical properties in context of the current research scenario. Further, it also explains the biocompatibility and toxicity of silver nanoparticles at cellular and molecular aspects. The mechanism of their toxicity has been described keeping in view of the recent research done. In brief, it reveals detail knowledge of the cellular and molecular impact of silver nanoparticles.

**Keywords:** silver nanoparticles, toxicology, oxidative stress, apoptosis

#### **1. Introduction**

Really revolutionary nanotech items, materials and application for example nanorobotics, are years long in the future. But what qualifies as "Nanotechnology" today is fundamental innovation that is going on in research centers everywhere throughout the world. Products of Nanotech which are on business sector today are generally steadily improved products (utilizing evolutionary nanotechnology) where some types of Nano-empowered materials (for example, Carbon nanotubes, nanocomposite structure of nanoparticles of specific substance) or nanotech process (for example Nano-patterning or Quantum Dots for medicinal imaging) is utilized in the assembling procedure. In their progressing and ongoing journey to improve existing products by making smaller parts and better execution materials, all at a lower cost, the number of organization that will make "Nano products" will become extremely fast and soon make up the most of all organization across numerous businesses.

Nanomaterials (NMs) have picked up noticeable quality in technological progressions due to their tunable synthetic, physical and organic properties with improved execution over their bulk counter partners. They are arranged depending on their origin, size, shape and composition. The capacity to anticipate the remarkable properties of NMs expand the estimation of each classification. Nanomaterials speak to an active/functioning area of research and techno-economic parts in numerous application areas. NMs are depicted as a material with a length of 1–1000 nm in at least one dimension [1]. In any case, a single globally acknowledge definition for NMs does not exist. The diverse association has a distinction in assessment in defining NMs. As indicated by the Environmental Protection Agency (EPA), NMs can display remarkable properties unique than the equal chemical compound in a bigger dimension [2]. The US Food and Administration (USFDA) likewise alludes to NMs as "materials that have at least one dimension dependent phenomena" [2]. The International Organization for Standardization (ISO) has depicted NMs as a "Materials with any external nanoscale measurement or having internal nanoscale surface structure" [2]. As of late, the British Standard Institution proposed the following definition for the scientific terms that have been utilized:


The nanoparticles shows remarkable chemical, physical and natural properties at nanoscale contrasted with their respective particles at higher scales. This phenomenon is because of a moderately bigger surface region to the volume, expand reactivity or stability in a synthetic procedure, improved mechanical strength and so forth. These properties of nanoparticles have prompted its utilization of different applications [3]. Nanoparticles have been utilized in medication (drug delivery), in food industries, gene delivery and Cancer therapy and so on [3]. The nanoparticles are of various size, structure and shape. It well may be tubular, conical, spherical,

**105**

**Figure 1.**

*nanotechnology, Paul Scherrer Institut).*

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

hollow core, cylindrical, spiral, flat and so forth or sporadic and contrast from 1 to 100 nm in size. Nanomaterials/or nanoparticles are utilized in an expansive range of use. Today they contained in numerous products and utilized in different technologies. Most Nano items created on an industrial scale are nanoparticle, in spite of the fact that they likewise emerge as by-products in the manufacturing of other materials [4, 5]. Explicit synthesis is utilized to create the different nanoparticles, coating composite and dispersion. Characterized production and reaction condition is pivotal in acquiring such size-dependent molecule. Particle shape, crystallinity, chemical composition and size can be constrained by pH- value, synthetic arrangement (chemical), temperature, procedure control and surface modification [5]. Two fundamental procedures are utilized to create nanoparticles: "Top-down"

and "Bottom-up". The expression "Top-down" alludes here to the mechanical squashing of source materials utilizing a milling procedure. In the "Bottom-up" strategy, structures are developed by the synthetic procedure. The determination of the individual procedure relies upon the compound organization and the desire

Strangely, the morphological parameters of NPs can be tweaked by shifting the chemical concentration and reaction condition for example pH and temperature. However, if these synthesized NMs are exposed to the real application, then they can experience the following impediment, which is stability in a threatening situation, absence of comprehension in fundamental mechanism and modeling factors, bioaccumulation or toxicity quality, extensive examination requirements recycle, reuse, regeneration. In true word, it is desirable that the properties, behavior and types of nanomaterials ought to be improved to meet the aforementioned points. Then again, these impediments are opening new and extraordinary opportunities in

To counter those restrictions a new era of green synthesis methodologies is increasing incredible in recent research and innovative work on material science and technologies. Essentially green synthesis will straightforwardly help uplift the ecological friendliness as they are generated through clean up, regulation/guideline, control and remediation process additionally there are few parts like the decrease of derivatives, decrease of contamination, prevention and minimalization of waste

*Methods of nanoparticles production: top-down and bottom-up (image: Laboratory for micro and* 

features indicated for the nanoparticles [6] (**Figure 1**) (**Table 1**).

*DOI: http://dx.doi.org/10.5772/intechopen.90717*

this developing field of research.

#### *Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

*Engineered Nanomaterials - Health and Safety*

differences [1, 3].

measurements [1, 3].

measurement [1, 3].

ture [1, 3].

measurements.

biomedical applications [1, 3].

speak to an active/functioning area of research and techno-economic parts in numerous application areas. NMs are depicted as a material with a length of 1–1000 nm in at least one dimension [1]. In any case, a single globally acknowledge definition for NMs does not exist. The diverse association has a distinction in assessment in defining NMs. As indicated by the Environmental Protection Agency (EPA), NMs can display remarkable properties unique than the equal chemical compound in a bigger dimension [2]. The US Food and Administration (USFDA) likewise alludes to NMs as "materials that have at least one dimension dependent phenomena" [2]. The International Organization for Standardization (ISO) has depicted NMs as a "Materials with any external nanoscale measurement or having internal nanoscale surface structure" [2]. As of late, the British Standard Institution proposed the following definition for the scientific terms that have been utilized:

• *Nanoscience*: The science and investigation of matter at the nanoscale that manages to understand their size and structure-dependent properties and compares at the rise of individual atoms or molecules or bulk materials related

• *Nanotechnology*: manipulation and control of matter on a nanoscale measurement by utilizing scientific logical knowledge of different industrial and

• *Nanomaterials*: Materials with any inside or outside structure on the nanoscale

• *Nano-objects*: Materials that have at least one or more peripheral nanoscale

• *Nanoparticles*: Nano-objects with three outer nanoscale measurements. The terms Nano rod or Nano plate are utilized, rather than nanoparticles (NP) when the longest and the shortest axes length of a nano-object are unique [1, 3].

• *Nanofiber*: When two comparable exterior nanoscale measurements and a third measurement are available in a nanomaterial, it is alluded to as a nanofiber [1, 3].

• *Nanocomposite*: Multiphase structure with at least one phase on the nanoscale

• *Nanostructure*: Composition of interconnected parts in the nanoscale area [1, 3].

• *Nanostructured materials*: Materials containing interior or surface nanostruc-

The nanoparticles shows remarkable chemical, physical and natural properties at nanoscale contrasted with their respective particles at higher scales. This phenomenon is because of a moderately bigger surface region to the volume, expand reactivity or stability in a synthetic procedure, improved mechanical strength and so forth. These properties of nanoparticles have prompted its utilization of different applications [3]. Nanoparticles have been utilized in medication (drug delivery), in food industries, gene delivery and Cancer therapy and so on [3]. The nanoparticles are of various size, structure and shape. It well may be tubular, conical, spherical,

• *Nanoscale*: Approximately 1–1000 nm size range [1, 3].

**104**

hollow core, cylindrical, spiral, flat and so forth or sporadic and contrast from 1 to 100 nm in size. Nanomaterials/or nanoparticles are utilized in an expansive range of use. Today they contained in numerous products and utilized in different technologies. Most Nano items created on an industrial scale are nanoparticle, in spite of the fact that they likewise emerge as by-products in the manufacturing of other materials [4, 5]. Explicit synthesis is utilized to create the different nanoparticles, coating composite and dispersion. Characterized production and reaction condition is pivotal in acquiring such size-dependent molecule. Particle shape, crystallinity, chemical composition and size can be constrained by pH- value, synthetic arrangement (chemical), temperature, procedure control and surface modification [5].

Two fundamental procedures are utilized to create nanoparticles: "Top-down" and "Bottom-up". The expression "Top-down" alludes here to the mechanical squashing of source materials utilizing a milling procedure. In the "Bottom-up" strategy, structures are developed by the synthetic procedure. The determination of the individual procedure relies upon the compound organization and the desire features indicated for the nanoparticles [6] (**Figure 1**) (**Table 1**).

Strangely, the morphological parameters of NPs can be tweaked by shifting the chemical concentration and reaction condition for example pH and temperature. However, if these synthesized NMs are exposed to the real application, then they can experience the following impediment, which is stability in a threatening situation, absence of comprehension in fundamental mechanism and modeling factors, bioaccumulation or toxicity quality, extensive examination requirements recycle, reuse, regeneration. In true word, it is desirable that the properties, behavior and types of nanomaterials ought to be improved to meet the aforementioned points. Then again, these impediments are opening new and extraordinary opportunities in this developing field of research.

To counter those restrictions a new era of green synthesis methodologies is increasing incredible in recent research and innovative work on material science and technologies. Essentially green synthesis will straightforwardly help uplift the ecological friendliness as they are generated through clean up, regulation/guideline, control and remediation process additionally there are few parts like the decrease of derivatives, decrease of contamination, prevention and minimalization of waste

#### **Figure 1.**

*Methods of nanoparticles production: top-down and bottom-up (image: Laboratory for micro and nanotechnology, Paul Scherrer Institut).*


#### **Table 1.**

*Categories of the nanoparticles synthesized from the various methods [1].*

and ultimately the utilization of more secure solvent during synthesis process as well as renewable stock. Green synthesis is required to stay away from the production of undesirable or unsafe products through the build-up of reliable, maintainable and eco-friendly methods. Green synthesis of metallic nanoparticles has been embraced to suit different organic material (for example, algae, bacteria, plant extract and fungi) (**Figure 2**)[7]. Among the accessible green methods of synthesis for metal and metal oxide NPs, usage of plant extract is a fairly straightforward and simple procedure to create nanoparticles at large scale with respect to fungi and bacteria mediated synthesis. Synthesis of metal and metal oxide NPs, plant biodiversity has been comprehensively considered to be because of the availability of effective phytochemicals in different plant extract, particular in leaves such as amide, flavones, phenols, terpenoids, ketones, ascorbic acid, aldehyde and carboxylic acids. These components are equipped of reducing metal salts into metal NPs [7, 8] (**Tables 2** and **3**).

**107**

**Table 3.**

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

**Species Nanoparticles Size** 

3 *E. coli* Cadmium 2–5 Fluorescent

Titanium dioxide

*Synthesis of metallic nanoparticles from various biological species (bacteria) [7].*

**Species Nanoparticles Size** 

**(nm)**

Iron oxide 40–50 Octahedral

Silver 23–105 Crystalline

**(nm)**

500

Gold 2–40 Hexagonal,

Gold, silver 10–30 Spherical,

57.91

Gold, silver 5–35 Spherical,

6 *Morus* (mulberry) Silver 15–20 Spherical Antimicrobial

Gold 6.75–

Gold 200–

6 *Coriolus versicolor* Silver 25–75 Spherical Water-soluble

8 *Phoma glomerata* Silver 60–80 Spherical Antimicrobial agent

Gold 20–50 Spherical Catalysis

labels

prism

spherical

12–15 Spherical Plant nutrient

**Morphology Application**

Gold, silver 4–15 Spherical Catalysis

Silver 20 Spherical Antibacterial

Gold 5–100 Irregular Detection and

Silver 5–30 Spherical Kill microbes

tetrahedral, icosahedral

triangular

Spherical, triangular

hexagonal

Gold 10–35 Spherical Biomedical field

Spherical, triangular

Silver 28–122 Spherical Optical receptor,

1 *Lactobacillus casei* Silver 20–50 Spherical Drug delivery,

**Morphology Application**

bio-labeling

Wurtzite structures

antimicrobial

**—**

metallic catalyst

Antimicrobial agent

fertilizer

Infrared-absorbing optical coating

> destruction of cancer cells

Labeling in structural biology, paints

activity

Cancer hyperthermia, optical coating

Drug delivery, tumor imaging

Remediation of toxic metal

*DOI: http://dx.doi.org/10.5772/intechopen.90717*

**Sr. no.**

2 *Desulfovibrio* 

4 *Klebsiella* 

5 *Aquaspirillum magnetotacticum*

7 *Penicillium* 

9 *Saccharomyces cerevisiae* broth

10 *Aspergillus flavus* TFR7

1 *Eucalyptus* 

2 *Cymbopogon* 

3 *Syzygium* 

4 *Mentha piperita*

5 *Medicago sativa*

7 *Aloe barbadensis* Miller(*Aloe vera*)

8 *Coriandrum* 

9 *Azadirachta indica* (neem)

10 *Terminalia catappa* (almond)

*citriodora* (neelagiri)

*flexuosus* (lemon grass)

*aromaticum* (clove buds)

(peppermint)

(alfalfa)

*sativum* (coriander)

*Synthesis of metallic nanoparticles from various plant extract [7].*

**Table 2.**

**Sr. no.** *desulfuricans*

*pneumonia*

*brevicompactum*

**Figure 2.** *Different methods for the synthesis of nanoparticles [4, 7].*


#### *Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

#### **Table 2.**

*Engineered Nanomaterials - Health and Safety*

**Category Method Nanoparticles**

Top-down Sputtering Metal based

*Categories of the nanoparticles synthesized from the various methods [1].*

Bottom-up Pyrolysis Carbon and metal oxide based

Nanolithography Metal based

Spinning Organic polymers

Chemical vapor deposition (CVD) Carbon and metal based

Biosynthesis Organic polymers and metal based

Sol-gel Carbon metal and metal oxide based

Laser ablation Carbon based and metal oxide based Thermal decomposition Carbon and metal oxide based

Mechanical milling Metal, oxide and metal oxide based

and ultimately the utilization of more secure solvent during synthesis process as well as renewable stock. Green synthesis is required to stay away from the production of undesirable or unsafe products through the build-up of reliable, maintainable and eco-friendly methods. Green synthesis of metallic nanoparticles has been embraced to suit different organic material (for example, algae, bacteria, plant extract and fungi) (**Figure 2**)[7]. Among the accessible green methods of synthesis for metal and metal oxide NPs, usage of plant extract is a fairly straightforward and simple procedure to create nanoparticles at large scale with respect to fungi and bacteria mediated synthesis. Synthesis of metal and metal oxide NPs, plant biodiversity has been comprehensively considered to be because of the availability of effective phytochemicals in different plant extract, particular in leaves such as amide, flavones, phenols, terpenoids, ketones, ascorbic acid, aldehyde and carboxylic acids. These components

are equipped of reducing metal salts into metal NPs [7, 8] (**Tables 2** and **3**).

**106**

**Figure 2.**

*Different methods for the synthesis of nanoparticles [4, 7].*

**Table 1.**

*Synthesis of metallic nanoparticles from various biological species (bacteria) [7].*


#### **Table 3.**

*Synthesis of metallic nanoparticles from various plant extract [7].*

## **2. Classification of nanoparticles**

#### **2.1 Organic nanoparticles**

Dendrimers, micelles, liposomes and ferritin are usually known as natural nanoparticles or polymers. These nanoparticles are biodegradable, non-toxic and a few particles for example, micelles and liposomes have a hollow center otherwise known as nanocapsules [9].

#### **2.2 Inorganic nanoparticles**

Inorganic nanoparticles are not comprised of carbon. Metal and metal oxide based nanoparticles are commonly classified as inorganic nanoparticles.


#### **2.3 Carbon based**

The nanoparticles made totally of carbon are known as carbon-based [1, 9, 10]. They can be classified as:


**109**

**Figure 3.**

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

agglomeration are seen as of 500 nm [1, 10].

• *Carbon black*: It is an undefined material comprised of carbon, generally spherical in shape with diameter measurements up to 20–70 nm. Interaction between the particles is high to such as an extent that they aggregate and the

Nano-technology has acquired an incredible revolution in the industrial division. Due to their exceptional physiochemical and electrical properties, Nanosized materials have increased a great deal of fascination in the field of hardware, biotechnology and aeronautic design. It is additionally being utilized in the field of medicine NPs similar to the novel delivery system for drugs, DNA and so on. Human is exposed to different non-scale materials since the new developing field of nanotechnology has turned into another danger to human life [11, 12]. The proposed hypothesis is that the NPs of size under 10 nm act similar to gas and can enter human tissues effectively and may abrogate the cell typical biochemical condition [11, 13]. There have been studies on human and murine models that the NPs are exposed through orally they are circulated to the spleen, liver, heart

*The following figure represents usages of nanotechnology/nanoparticles in different field [6].*

*DOI: http://dx.doi.org/10.5772/intechopen.90717*

**3. Nanoparticle as a threat**

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

• *Carbon black*: It is an undefined material comprised of carbon, generally spherical in shape with diameter measurements up to 20–70 nm. Interaction between the particles is high to such as an extent that they aggregate and the agglomeration are seen as of 500 nm [1, 10].

#### **3. Nanoparticle as a threat**

*Engineered Nanomaterials - Health and Safety*

**2. Classification of nanoparticles**

Dendrimers, micelles, liposomes and ferritin are usually known as natural nanoparticles or polymers. These nanoparticles are biodegradable, non-toxic and a few particles for example, micelles and liposomes have a hollow center otherwise

Inorganic nanoparticles are not comprised of carbon. Metal and metal oxide

• *Metal based*: Nanoparticles that are integrated from metals to Nano size either by ruinous or constructive strategies are metal based nanoparticles [1, 9]. Practically every one of metal can be synthesized into their nanoparticles. The normally utilized metals for nanoparticles are aluminum, cobalt, gold, silver, zinc, iron, copper, and cobalt [1, 9]. Nanoparticles have a distinctive size

• *Metal oxides based*: The metal oxides based nanoparticles are orchestrated to

• *Cerium oxide*: These nanoparticles have excellent properties when contrasted with their metal partner. For example, zinc oxide. Iron oxide, silicon dioxide,

The nanoparticles made totally of carbon are known as carbon-based [1, 9, 10].

• *Fullerenes*: Fullerenes is a carbon particle that is spherical on shape and made

• *Graphene*: Graphene is an allotrope of carbon. It is a hexagonal system of

carbon atoms form the spherical structure with diameter of 8.2 nm for a single

honeycomb lattice made of carbon atoms in a 2-D planar surface. The thickness

• *Carbon nano tubes*: In this, nano foil which has a honeycomb lattice of carbon atoms is twisted into a hollow cylinder to frame nanotubes of measurements as

• *Carbon nanofiber*: When graphene nano foil used to produce carbon nanofiber as carbon nanotubes however twisted into a cone or cup shape than a regular

hybridization. Around 28–1500

adjust the properties of their respective metal based nanoparticles.

based nanoparticles are commonly classified as inorganic nanoparticles.

**2.1 Organic nanoparticles**

known as nanocapsules [9].

**2.2 Inorganic nanoparticles**

magnetite, etc.

They can be classified as:

**2.3 Carbon based**

extends from 10 nm to 100 nm.

up of carbon molecules held together by sp2

of the graphene is of 1 nm [9, 10].

low as 0.7 nm [1, 10].

cylindrical tube [1, 10].

layer and for a multi-layered fullerenes 4–36 nm [9, 10].

**108**

Nano-technology has acquired an incredible revolution in the industrial division. Due to their exceptional physiochemical and electrical properties, Nanosized materials have increased a great deal of fascination in the field of hardware, biotechnology and aeronautic design. It is additionally being utilized in the field of medicine NPs similar to the novel delivery system for drugs, DNA and so on. Human is exposed to different non-scale materials since the new developing field of nanotechnology has turned into another danger to human life [11, 12]. The proposed hypothesis is that the NPs of size under 10 nm act similar to gas and can enter human tissues effectively and may abrogate the cell typical biochemical condition [11, 13]. There have been studies on human and murine models that the NPs are exposed through orally they are circulated to the spleen, liver, heart

and lungs also to the brain and gastrointestinal zone, some other exposure routes may incorporate skin, ingestion, inhalation and injection. Some designed NPs are being utilized in many products with direct exposure to people, for instance, ZnO NPs are added to numerous items including cotton texture, Food packaging and rubber for its freshening up and antibacterial attributes, TiO2 NPs are utilized in food coloring, makeup, skincare item and tattoo pigments, Fe2O3 NPs utilized in the final polish on metallic gems (jewelries) [12]. It has been seen that life expectancy of the nanoparticles in human is around 700 days in which it reliably has a risk to the body. Nanoparticles have an incredible risk to human's wellbeing when contrasted with large-sized particles of the similar chemical compound and it is commonly said that toxicities are contrarily corresponding to the size of the nanoparticles [14, 15]. As the utilization of engineered nanoparticles keeps on developing exponentially, an unintended and intended exposure may happen, which will prompt a high level of human wellbeing hazard. End product users, occupationally exposed subjects and the overall population may be in danger of antagonistic impact (**Figure 3**).

The physiochemical properties of NPs impact how they interact with cells and thus, their potential danger. Studies have demonstrated the different properties that make some nanoparticles more toxic than others. Hypothetically, molecules size is likely to add to cytotoxicity. Smaller NPs have a bigger specific surface area and thus in this way increasingly accessible surface area to interact with cell components for example, carbohydrates, protein, nucleic acids and fatty acids. Nanoparticles with small size are liable to enter the cells, causing cellular damage. Some nanoparticles lethality were seen as a function of both size and specific surface area. It has additionally been seen that size of NPs has seen to correspond with reactive oxygen species (ROS) generation when comparing the amount of ROS generation per surface area within certain size range [14–16]. Nanoparticles size between 10 nm or > 30 nm creates comparable level of ROS per surface area. In any case, there was a sensational increment in ROS production per unit surface in particle expanding from 10 to 30 nm. This information or data disclose to us the bits of knowledge with respect to the perplexing connection between NPs properties and Nano toxicity.

#### **4. Toxicity of silver nanoparticles**

Silver nanoparticles are progressively utilized in different fields, including health care, medical, food, consumer and industrial purpose because of their novel physical and chemical properties. Because of their unconventional properties, they have been utilized for a few applications, as in medical device coating, drug delivery, health care products, and food industry, as anticancer agent and orthopedics and also as anti-bacterial agents. AgNPs by a long shot the most generally utilized in customers items, for example, in kitchen utensils, toothpaste, bedding, deodorants, nursing bottles, washing machines, nipples and humidifiers [17]. So as to satisfy the necessity of silver NPs different strategy have been utilized for synthesis, conventional technique like chemical and physical strategies have been utilized, yet they are by all accounts expensive and toxic/hazardous [18].

An organic methodology has been utilized in the synthesis of AgNPs utilizing microorganisms, fungi and plant extract prompting to reliable alterative to chemical and physical techniques in acquiring the nanoparticles in controlled particle size. It has been seen that green synthesis of AgNPs with various stabilizing agents, for example, polyethylene glycol, alcohol vinyl, dextran, cyclodextrins and utilizing

**111**

**Figure 4.**

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

body weight of AgNPs may cause liver harm (**Figure 4**).

"andeli" (rose extract) [19–22]. This expands utilization of AgNPs in different materials has prompted a more straightforward and direct exposure in human and raised potential dangers to health issues. In an in vivo examination (Sprague-Dawley rodents) they were dealt with orally for 28 days with AgNPs in spite of the fact that there was no observable difference in clinical sign and neither in any difference in body or organ weight. The impacts on blood biochemistry have been seen to increase in cholesterol at high doses of AgNP which indicates that hepatotoxicity and increment in alkaline phosphatase. In another investigation, F344 rodents were fed AgNPs for a time period of 90 days and a decrease in body weight in males was seen following a month of exposure and a dose-dependent change was seen in cholesterolemia and alkaline phosphatases activity which proposed that 125 mg/kg

It is commonly realized that NPs can be absorbed by the digestive tract not just through the M-cells in the Peyer's patch yet additionally by numerous organs as shown in **Figure 5**. Culture of human mesenchymal stem cells incubated with

nanoparticles or human glioblastoma cells starch incubated with capped silver

capped AgNPs has been demonstrated to be more genotoxic than polysaccharidecapped AgNPs. Silver nanoparticles exposed to in vivo models like mice were seen to be more toxic than fish to capped AgNPs. However NPs toxicity/genotoxicity was seen as more when the concentration of albumin-capped NPs was increased to

In recent investigation, it has been seen that hepatotoxicity, pulmonary inflammation, genotoxicity, neurotoxicity, inflammatory effects and cytotoxicity have been related with various shape and size of silver nanoparticles. A large number of articles have been proposed that silver nanoparticles assume a noteworthy job in prompting Reactive Oxygen Species (ROS) which in returns lead to cell cytotoxicity and genotoxicity. It has been seen that cytotoxicity has been closely identified to the generation of ROS. For example interaction of AgNPs with mitochondrial can be seen that: 95% of the cell's energy is generated by mitochondria as it is the powerhouse of the cells. It's a significant and essential piece of the cell. ROS generation is possible because of the superoxide spillage through the membrane. The interaction of AgNPs with mitochondria which prompts generation of ROS can be clarified in a

cysteine residues. AgNPs disrupts the membrane proteins integrity of the mitochondria, also hampers the membrane permeability of the membrane and abrogate

and silver nanoparticles have a high affinity (−SH) thiol group in

nanoparticle (AgNPs) showed genotoxicity up to dosages of 50 μg ml<sup>−</sup><sup>1</sup>

of normal human lungs fibroblast cells or albumin-capped silver

. Albumin-

*DOI: http://dx.doi.org/10.5772/intechopen.90717*

0.1 μg ml<sup>−</sup><sup>1</sup>

>100 μg ml<sup>−</sup><sup>1</sup>

manner when Ag+

(**Table 4**).

the mitochondrial functions (**Figure 6**).

*Nanoparticles pathway and toxicological impact [13, 14].*

#### *Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

*Engineered Nanomaterials - Health and Safety*

antagonistic impact (**Figure 3**).

Nano toxicity.

**4. Toxicity of silver nanoparticles**

are by all accounts expensive and toxic/hazardous [18].

and lungs also to the brain and gastrointestinal zone, some other exposure routes may incorporate skin, ingestion, inhalation and injection. Some designed NPs are being utilized in many products with direct exposure to people, for instance, ZnO NPs are added to numerous items including cotton texture, Food packaging and rubber for its freshening up and antibacterial attributes, TiO2 NPs are utilized in food coloring, makeup, skincare item and tattoo pigments, Fe2O3 NPs utilized in the final polish on metallic gems (jewelries) [12]. It has been seen that life expectancy of the nanoparticles in human is around 700 days in which it reliably has a risk to the body. Nanoparticles have an incredible risk to human's wellbeing when contrasted with large-sized particles of the similar chemical compound and it is commonly said that toxicities are contrarily corresponding to the size of the nanoparticles [14, 15]. As the utilization of engineered nanoparticles keeps on developing exponentially, an unintended and intended exposure may happen, which will prompt a high level of human wellbeing hazard. End product users, occupationally exposed subjects and the overall population may be in danger of

The physiochemical properties of NPs impact how they interact with cells and thus, their potential danger. Studies have demonstrated the different properties that make some nanoparticles more toxic than others. Hypothetically, molecules size is likely to add to cytotoxicity. Smaller NPs have a bigger specific surface area and thus in this way increasingly accessible surface area to interact with cell components for example, carbohydrates, protein, nucleic acids and fatty acids. Nanoparticles with small size are liable to enter the cells, causing cellular damage. Some nanoparticles lethality were seen as a function of both size and specific surface area. It has additionally been seen that size of NPs has seen to correspond with reactive oxygen species (ROS) generation when comparing the amount of ROS generation per surface area within certain size range [14–16]. Nanoparticles size between 10 nm or > 30 nm creates comparable level of ROS per surface area. In any case, there was a sensational increment in ROS production per unit surface in particle expanding from 10 to 30 nm. This information or data disclose to us the bits of knowledge with respect to the perplexing connection between NPs properties and

Silver nanoparticles are progressively utilized in different fields, including health care, medical, food, consumer and industrial purpose because of their novel physical and chemical properties. Because of their unconventional properties, they have been utilized for a few applications, as in medical device coating, drug delivery, health care products, and food industry, as anticancer agent and orthopedics and also as anti-bacterial agents. AgNPs by a long shot the most generally utilized in customers items, for example, in kitchen utensils, toothpaste, bedding, deodorants, nursing bottles, washing machines, nipples and humidifiers [17]. So as to satisfy the necessity of silver NPs different strategy have been utilized for synthesis, conventional technique like chemical and physical strategies have been utilized, yet they

An organic methodology has been utilized in the synthesis of AgNPs utilizing microorganisms, fungi and plant extract prompting to reliable alterative to chemical and physical techniques in acquiring the nanoparticles in controlled particle size. It has been seen that green synthesis of AgNPs with various stabilizing agents, for example, polyethylene glycol, alcohol vinyl, dextran, cyclodextrins and utilizing

**110**

"andeli" (rose extract) [19–22]. This expands utilization of AgNPs in different materials has prompted a more straightforward and direct exposure in human and raised potential dangers to health issues. In an in vivo examination (Sprague-Dawley rodents) they were dealt with orally for 28 days with AgNPs in spite of the fact that there was no observable difference in clinical sign and neither in any difference in body or organ weight. The impacts on blood biochemistry have been seen to increase in cholesterol at high doses of AgNP which indicates that hepatotoxicity and increment in alkaline phosphatase. In another investigation, F344 rodents were fed AgNPs for a time period of 90 days and a decrease in body weight in males was seen following a month of exposure and a dose-dependent change was seen in cholesterolemia and alkaline phosphatases activity which proposed that 125 mg/kg body weight of AgNPs may cause liver harm (**Figure 4**).

It is commonly realized that NPs can be absorbed by the digestive tract not just through the M-cells in the Peyer's patch yet additionally by numerous organs as shown in **Figure 5**. Culture of human mesenchymal stem cells incubated with 0.1 μg ml<sup>−</sup><sup>1</sup> of normal human lungs fibroblast cells or albumin-capped silver nanoparticles or human glioblastoma cells starch incubated with capped silver nanoparticle (AgNPs) showed genotoxicity up to dosages of 50 μg ml<sup>−</sup><sup>1</sup> . Albumincapped AgNPs has been demonstrated to be more genotoxic than polysaccharidecapped AgNPs. Silver nanoparticles exposed to in vivo models like mice were seen to be more toxic than fish to capped AgNPs. However NPs toxicity/genotoxicity was seen as more when the concentration of albumin-capped NPs was increased to >100 μg ml<sup>−</sup><sup>1</sup> (**Table 4**).

In recent investigation, it has been seen that hepatotoxicity, pulmonary inflammation, genotoxicity, neurotoxicity, inflammatory effects and cytotoxicity have been related with various shape and size of silver nanoparticles. A large number of articles have been proposed that silver nanoparticles assume a noteworthy job in prompting Reactive Oxygen Species (ROS) which in returns lead to cell cytotoxicity and genotoxicity. It has been seen that cytotoxicity has been closely identified to the generation of ROS. For example interaction of AgNPs with mitochondrial can be seen that: 95% of the cell's energy is generated by mitochondria as it is the powerhouse of the cells. It's a significant and essential piece of the cell. ROS generation is possible because of the superoxide spillage through the membrane. The interaction of AgNPs with mitochondria which prompts generation of ROS can be clarified in a manner when Ag+ and silver nanoparticles have a high affinity (−SH) thiol group in cysteine residues. AgNPs disrupts the membrane proteins integrity of the mitochondria, also hampers the membrane permeability of the membrane and abrogate the mitochondrial functions (**Figure 6**).

**Figure 4.** *Nanoparticles pathway and toxicological impact [13, 14].*

#### **Figure 5.**

*Main target organ of silver nanoparticles.*

#### **Figure 6.**

*This figure represents the endogenous ROS production, which are involved in oxidative stress. Interaction between mitochondrial and AgNP generate ROS from mitochondria which leads to cell death [23].*

A great deal of studies has demonstrated a connection in ROS generation by silver nanoparticles, oxidative stress and cytotoxicity. Numerous toxicological changes have been reported in embryos when they are exposed to nanoparticles, for example, changes in oxidative stress markers such as apoptosis, changes in expression of genes and lipid oxidation, etc. It has been seen that massive production of free radicals lead to the generation of pro-inflammatory cytokines and furthermore initiation of NOX/

**113**

**Sr. no.**

1 2 3 4 5 6 7 8 9 10 **Table 4.** *In vivo cytotoxicity and genotoxicity effects of AgNPs in different organisms [25].*

Vertebrate/chordata/

HepG2

15–20

13 μg ml−1 (58% survival)

Human hepatocytes

150 cell per group

mammalian, human

Vertebrates/chordata/

mammalian, human

Vertebrate/chordata/

mammalian

Vertebrate/chordata/fish

Primary trout

35

hepatocytes

N = 3, each

treatement

MEF

25

50 μg ml−1

50 μg ml−1 this concentration upregulates the Rad51 and phosphorylates-H2AX expression and also upregulates p53

Mouse embryonic

fibroblasts

Human lymphocytes

25–45

Till 400 μg ml−1

Till 50 μg ml−1 no DNA damage

Here it was indicated that the AGNPs induces ROS-induced nontoxicity

Plantae/liliopsida

Vertebrate/chordata/

mammalian

Vertebrate/chordata/fish

Vertebrate/chordata/

mammalian

Vertebrate/chordata/

mammalian, human

Vertebrate/chordata/

IMR-90

6–20

50 μg ml−1

Human lung

fibroblast

A549

78

12.5 μg ml−1

Human lung carc.

mES

25

50 μg ml−1

Mouse embryonic

stem cells

OLHN12

20–30

1.3 μg ml−1

Medaka fish

BRL 3A

25

50 μg ml−1

Rat liver cells

*Allium cepa*

24–55

ROS-induced up to 10 μg ml−1cell

death and DNA damage doses

20 μg ml−1

Significant toxicity from

500–1000 μg ml−1

5000 cells

mammalian

**Classification**

**Cell**

**Size (nm)**

**Cytotoxicity**

**Genotoxicity**

Comet assay 5 μm

(50 comets were analyzed per concentration) (DNA damage at 50 μg ml−1

In this it was indicated that silver NPs mediated ROS-induced genotoxicity

50 μg ml−1 (this conc. upregulates the DNA damage repair proteins Rad51

and phosphorylated-H2AX expression and even upregulates cell cycle

checkpoint protein p53)

1.2 μg ml−1 aneuplidy 15.8%

10 μg ml−1

No genotoxicity

Didn't cause significant lactate dehydrogenase release

)

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

*DOI: http://dx.doi.org/10.5772/intechopen.90717*


#### *Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

*Engineered Nanomaterials - Health and Safety*

**112**

**Figure 6.**

**Figure 5.**

*Main target organ of silver nanoparticles.*

A great deal of studies has demonstrated a connection in ROS generation by silver

nanoparticles, oxidative stress and cytotoxicity. Numerous toxicological changes have been reported in embryos when they are exposed to nanoparticles, for example, changes in oxidative stress markers such as apoptosis, changes in expression of genes and lipid oxidation, etc. It has been seen that massive production of free radicals lead to the generation of pro-inflammatory cytokines and furthermore initiation of NOX/

*This figure represents the endogenous ROS production, which are involved in oxidative stress. Interaction between mitochondrial and AgNP generate ROS from mitochondria which leads to cell death [23].*

> **Table 4.**

#### **Figure 7.**

*Pictorial representation of activation of cellular mechanisms of inflammatory signal when exposed to AgNP generated from ROS and by strengthening of NADPH oxidase activity. By MAP kinases pathway, activation of oxidative IKK-B which is induced by stress leads to NF-kB translocation and expression of marker and potential mediators of inflammation increases, mitochondrial damage and membrane damage which can cause toxicity in cell and leads to death by apoptosis [24].*

NADPH oxidase family. It must be noticed that other than inflammatory effects of oxygen radicals, oxidants helps the release of inflammatory mediators by activating transcription factor including AP-1, hypoxia inducing factor and NF-kB and which prompts to oxidative stress and inflammation. Oxidative stress might have a double role, first as "effector" (by oxidant discharge and induced toxicity) and secondly as "modulator" (managing transcription factor) of chronic micro-inflammation process. This interaction among inflammation and oxidative stress in an amplified manner may prompt to the deleterious impacts brought by silver nanoparticles and which can prompt to DNA damage and cell demise by apoptosis (**Figure 7**).

#### **5. Conclusion**

In brief, the ingenious and extensive demand of nanoparticles has led to their extensive production. After use modalities path their way towards exposure to environment as well as to the human health moreover the product which are being used are also in direct contact with the human tissue. Prolong accumulation of the nanoparticle particularly talking about silver nanoparticles.

**115**

**Author details**

Hazaribagh, India

, Puja Kumari<sup>2</sup>

provided the original work is properly cited.

, Suresh K. Verma1

2 Advance Science and Technology Research Centre, Vinoba Bhave University,

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 School of Biotechnology, KIIT University, Bhubaneswar, India

\*Address all correspondence to: amallick1@rediffmail.com

and M. Anwar Mallick<sup>2</sup>

\*

Paritosh Patel1

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles*

*DOI: http://dx.doi.org/10.5772/intechopen.90717*

*Cellular and Molecular Impact of Green Synthesized Silver Nanoparticles DOI: http://dx.doi.org/10.5772/intechopen.90717*

## **Author details**

*Engineered Nanomaterials - Health and Safety*

*toxicity in cell and leads to death by apoptosis [24].*

NADPH oxidase family. It must be noticed that other than inflammatory effects of oxygen radicals, oxidants helps the release of inflammatory mediators by activating transcription factor including AP-1, hypoxia inducing factor and NF-kB and which prompts to oxidative stress and inflammation. Oxidative stress might have a double role, first as "effector" (by oxidant discharge and induced toxicity) and secondly as "modulator" (managing transcription factor) of chronic micro-inflammation process. This interaction among inflammation and oxidative stress in an amplified manner may prompt to the deleterious impacts brought by silver nanoparticles and

*Pictorial representation of activation of cellular mechanisms of inflammatory signal when exposed to AgNP generated from ROS and by strengthening of NADPH oxidase activity. By MAP kinases pathway, activation of oxidative IKK-B which is induced by stress leads to NF-kB translocation and expression of marker and potential mediators of inflammation increases, mitochondrial damage and membrane damage which can cause* 

which can prompt to DNA damage and cell demise by apoptosis (**Figure 7**).

nanoparticle particularly talking about silver nanoparticles.

In brief, the ingenious and extensive demand of nanoparticles has led to their extensive production. After use modalities path their way towards exposure to environment as well as to the human health moreover the product which are being used are also in direct contact with the human tissue. Prolong accumulation of the

**114**

**5. Conclusion**

**Figure 7.**

Paritosh Patel1 , Puja Kumari<sup>2</sup> , Suresh K. Verma1 and M. Anwar Mallick<sup>2</sup> \*

1 School of Biotechnology, KIIT University, Bhubaneswar, India

2 Advance Science and Technology Research Centre, Vinoba Bhave University, Hazaribagh, India

\*Address all correspondence to: amallick1@rediffmail.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[2] Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations. Beilstein Journal of Nanotechnology. 3 Apr 2018;**9**:1050-1074. DOI: 10.3762/bjnano.9.98

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cellulose nanocrystal-supported gold nanoparticles with enhanced catalytic performance. Environmental Science. Nano. 2014;**1**:71-79. DOI: 10.1039/

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[15] Gálvez Pérez V, Gózalo CT, Leite PEC, Pereira MR, Granjeiro JM, Alkilany AM, et al. Toxicología de las nanopartículas. Revista Complutense de Ciencias Veterinarias. 2015;**33**:2313- 2333. DOI: 10.1016/j.addr.2011.09.001

[16] Liu R, Rallo R, George S, Ji Z, Nair S, Nel AE, et al. Classification NanoSAR development for cytotoxicity of metal oxide nanoparticles. Small. 2011;**7**:1118- 1126. DOI: 10.1002/smll.201002366

[17] Zhang XF, Liu ZG, Shen W, Gurunathan S. Silver nanoparticles: Synthesis, characterization, properties, applications, and therapeutic approaches. International Journal of Molecular Sciences. 2016;**17**. DOI: 10.3390/ijms17091534

[18] Akter M, Sikder MT, Rahman MM, Ullah AKMA, Hossain KFB, Banik S, et al. A systematic review on silver nanoparticles-induced cytotoxicity: Physicochemical properties and perspectives. Journal of Advanced Research. 2018;**9**:1-16. DOI: 10.1016/j. jare.2017.10.008

[19] Erdogan O, Abbak M, Demirbolat GM, Birtekocak F, Aksel M, Pasa S, et al. Green synthesis of silver nanoparticles via Cynara scolymus leaf extracts: The characterization, anticancer potential with photodynamic therapy in MCF7 cells. PLoS One. 2019;**14**:1-15. DOI: 10.1371/journal. pone.0216496

[20] Wu X, Lu C, Zhou Z, Yuan G, Xiong R, Zhang X. Green synthesis and formation mechanism of cellulose nanocrystal-supported gold nanoparticles with enhanced catalytic performance. Environmental Science. Nano. 2014;**1**:71-79. DOI: 10.1039/ c3en00066d

[21] Roy A, Bulut O, Some S, Mandal AK, Yilmaz MD. Green synthesis of silver nanoparticles: Biomolecule-nanoparticle organizations targeting antimicrobial activity. RSC Advances. 2019;**9**:2673-2702. DOI: 10.1039/c8ra08982e

[22] Arshad A. Bacterial synthesis and applications of nanoparticles. Journal of Nanoscience and Nanotechnology. 2017;**11**:119

[23] Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini Review. DOI: 10.1002/jat.3654

[24] Silver nanoparticles: Their potential toxic effects after oral exposure and underlying mechanisms—A review. DOI: 10.1016/j.fct.2014.12.019

[25] Silver nanoparticles: A brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles. DOI: 10.1002/jat.2780

**116**

*Engineered Nanomaterials - Health and Safety*

[1] Ealias AM, Saravanakumar MP. A review on the classification, characterisation, synthesis of

**References**

nanoparticles and their application. IOP Conference Series: Materials Science and Engineering. 2017;**263**:032019. DOI: 10.1088/1757-899X/263/3/032019

[8] Kumari P, Panda PK, Jha E,

to ROS and Apoptosis regulated cytotoxicity inferred by green synthesized CuO nanoparticles from *Calotropis gigantea* to embryonic Zebrafish. Scientific Reports. 2017: 1-17. DOI: 10.1038/s41598-017-16581-1.

[9] Grose A, Grose A. What are the different types of therapy? In: Are You Considering Therapy. 2018. pp. 1-96. DOI: 10.4324/9780429471940-1

[10] Narendra Kumar SK. Essentials in nanoscience and nanotechnology. Carbon-Based Nanomaterials. John Wiley & Sons, Inc; 16 Mar 2016. Print ISBN: 9781119096115, Online ISBN: 9781119096122. DOI: 10.1002/9781119096122. Chapter 5

[11] Huang YW, Cambre M, Lee HJ. The toxicity of nanoparticles depends on multiple molecular and physicochemical mechanisms. International Journal of Molecular Sciences. Dec 2017;**18**(12):2702.

[12] Bahadar H, Maqbool F, Niaz K, Abdollahi M. Toxicity of nanoparticles

Biomedical Journal. 2016;**20**:1-11. DOI:

[13] De Matteis V, Rinaldi R. Toxicity assessment in the nanoparticle era. Advances in Experimental Medicine and Biology. 2018;**1048**:1-19. DOI: 10.1007/978-3-319-72041-8\_1

Sokolov P, Berestovoy M, Karaulov A, Nabiev I. Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Research Letters. 7 Feb 2018;**13**(1):44. DOI: 10.1186/

[14] Sukhanova A, Bozrova S,

s11671-018-2457-x

DOI: 10.3390/ijms18122702

and an overview of current experimental models. Iranian

10.7508/ibj.2016.01.001

Article number: 16284

Kumari K, Nisha K. Mechanistic insight

[2] Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations. Beilstein Journal of Nanotechnology. 3 Apr 2018;**9**:1050-1074.

DOI: 10.3762/bjnano.9.98

2015;**4**:379-386

[3] Heera P, Shanmugam S. Review article nanoparticle characterization and application: An overview.

Hofmann T. Nanoparticles: Structure, properties, preparation and behaviour in nanoparticles: Structure, properties,

environmental media. Ecotoxicology. Jul 2008;**17**(5):326-343. DOI: 10.1007/

[4] Christian P, Baalousha M,

preparation and behaviour in

[5] Prakash Sharma V, Sharma U, Chattopadhyay M, Shukla VN. Advance applications of nanomaterials: A review. Materials Today: Proceedings. 2018;**5**:6376-6380. DOI: 10.1016/j.

[6] Zielonka A, Klimek-ochab M. Fungal synthesis of size-

10.1088/2043-6254/aa84d4

Samddar P, Kumar P. Green synthesis of metals and their oxide nanoparticles: Applications for

10.1186/s12951-018-0408-4

defined nanoparticles. Advances in Natural Sciences: Nanoscience and Nanotechnology. 2017;**8**:043001. DOI:

[7] Singh J, Dutta T, Kim KH, Rawat M,

environmental remediation. Journal of Nanobiotechnology. 2018;**16**:1-24. DOI:

s10646-008-0213-1

matpr.2017.12.248

**119**

opment (**Figure 1**).

**Chapter 7**

**Abstract**

diagnosis

**1. Introduction**

Theranostic Nanoparticles and

Nanoparticles offer a lot of advantageous backgrounds for many applications due to their physical, chemical and biological properties. Their different composition (metals, lipids, polymers, peptides) and shapes (spheres, rods, pyramids, flowers and so on) are influenced by the synthesis methods and functionalization procedures. However, in the medical field, researchers focus on the biocompatibility and biodegradability of the nanoparticles in their attempts for a targeted therapy in which the nanocarriers need to bypass certain biological barriers. Moreover, the increased interest in molecular imaging has brought nanoparticles in the spotlight for their applications in two distinct directions: therapy and diagnosis. Furthermore, recent advances in nanoparticle designs have introduced novel nano-objects suitable as both detection and delivery systems at the same time, thus

**Keywords:** nanoparticles, nano-oncology, targeted therapy, molecular imaging,

Nanomedicine is able to study the organism and especially the disease at the nanoscale level and offers a lot of structural and functional information for the development of new therapeutics and diagnosis strategies [1]. Nano-oncology refers

Oncological malignancies affect worldwide population with an incidence of 18.1 million new cancer cases and 9.6 million cancer deaths (GLOBOCAN 2018). Usually, the most used treatment scheme is surgery, radiotherapy and chemotherapy. These strategies are not very efficient because it does not only affect the disease site, but healthy tissues too, and in many cases, cancer can develop therapy resistance [2]. Nanotechnology tools have potential to overcome the side effects and the inefficiency of some therapies. Due to its small size, nanoparticles (NPs) can be used for molecular characterization of the disease, and based on this, it can contribute to discover new therapies. Moreover, various oncological chemotherapeutics are

Besides drug encapsulation, NPs can be used for the delivery of growth factors

and other compounds applied in tissue engineering. On the other hand, NPs' properties are advantageous for new sensing and molecular imaging tools devel-

to the applications of nanotechnology in the oncology medical field.

nanoformulated and now are involved in clinical trials [3].

Their Spectrum in Cancer

*Anca Onaciu, Ancuta Jurj, Cristian Moldovan* 

*and Ioana Berindan-Neagoe*

providing theranostic applications.

#### **Chapter 7**
