**2. Nanoorganometallic complexes**

Recent advances suggest that nanotechnology will give a better solution for disease prevention, diagnosis, and treatment. It is an ideal targeting system, should have long circulating time, be present at appropriate concentrations at the target site, and should not lose its activity or therapeutic efficacy while in circulation. The increased vascular permeability coupled with an impaired lymphatic drainage in tumor allows an enhanced permeability and retention effect of the nanosystems in the tumor or inflamed tissue. Nanotechnology offers a solution for using the numerous chemical entities for treating brain disorders that are not clinically useful because of the presence of the blood-brain barrier.

The advantage of nanoparticles with potential MRI-related medical applications comprise of various materials, such as metals (gold, silver, and cobalt) or metal oxides (Fe<sup>3</sup> O4 , TiO2 and SiO2 ) (**Figure 2**). Magnetic nanoparticles coated with dimercapto succinic acid (DMSA) were toxic to neurons in a dose-dependent manner. Cobalt (Co), gold (Au@Fe), and platinum (Pt@ Fe) are the other types of nanomaterials that show potential application in antimicrobial and anticancer treatment. Several studies on nanoparticles shown them to be cytotoxic [72], genotoxic [73], and potentially carcinogenic [74] and are used to induce apoptosis and inhibit cell proliferation [75].

These nanomaterials contain the sphere and core-shell structures, two-dimensional (2D) grapheme nanosheets have great potential for high drug loading efficiency and conjugation of proteins, drugs, and fluorescent probes.

The molecular imaging applies to various techniques such as positron emission tomography (PET), computed tomography (CT), or ultrasound and magnetic resonance imaging (MRI) which gives the best spatial resolution and is either noninvasive or minimally invasive. As MRI is not applied in full potential due to low specificity, so it can be alternatively taken to use as cell markers. The unique paramagnetic and superparamagnetic properties of nanoparticles (NP) can be utilized for the detection with MRI in small quantities. Nanoparticles with potential MRI-related medical applications comprise various materials, such as metals (gold,

**Figure 2.** Schematic representation of the targeted contrast agent used for MRI approaching of the cancer cell and specific proteins.

silver, and cobalt) or metal oxides (Fe<sup>3</sup> O4 , TiO2 , and SiO2 ). While diagnostic is a common medical application of nanoparticles, they can also be used for therapy [76–80] (**Figure 3**).

Nanoparticles can be categorized in two parts:

**1.** Protect drug from degradation

8 Recent Progress in Organometallic Chemistry

**4.** Ease of drug targeting due to nanosize

**8.** Improve the oral bioavailability of the agents

**2. Nanoorganometallic complexes**

of proteins, drugs, and fluorescent probes.

**9.** Passive targeting of drugs to the macrophages (liver and spleen)

useful because of the presence of the blood-brain barrier.

Recent advances suggest that nanotechnology will give a better solution for disease prevention, diagnosis, and treatment. It is an ideal targeting system, should have long circulating time, be present at appropriate concentrations at the target site, and should not lose its activity or therapeutic efficacy while in circulation. The increased vascular permeability coupled with an impaired lymphatic drainage in tumor allows an enhanced permeability and retention effect of the nanosystems in the tumor or inflamed tissue. Nanotechnology offers a solution for using the numerous chemical entities for treating brain disorders that are not clinically

The advantage of nanoparticles with potential MRI-related medical applications comprise of

These nanomaterials contain the sphere and core-shell structures, two-dimensional (2D) grapheme nanosheets have great potential for high drug loading efficiency and conjugation

The molecular imaging applies to various techniques such as positron emission tomography (PET), computed tomography (CT), or ultrasound and magnetic resonance imaging (MRI) which gives the best spatial resolution and is either noninvasive or minimally invasive. As MRI is not applied in full potential due to low specificity, so it can be alternatively taken to use as cell markers. The unique paramagnetic and superparamagnetic properties of nanoparticles (NP) can be utilized for the detection with MRI in small quantities. Nanoparticles with potential MRI-related medical applications comprise various materials, such as metals (gold,

) (**Figure 2**). Magnetic nanoparticles coated with dimercapto succinic acid (DMSA) were toxic to neurons in a dose-dependent manner. Cobalt (Co), gold (Au@Fe), and platinum (Pt@ Fe) are the other types of nanomaterials that show potential application in antimicrobial and anticancer treatment. Several studies on nanoparticles shown them to be cytotoxic [72], genotoxic [73], and potentially carcinogenic [74] and are used to induce apoptosis and inhibit cell

O4 , TiO2

and

various materials, such as metals (gold, silver, and cobalt) or metal oxides (Fe<sup>3</sup>

**5.** Allow delivery of insoluble drugs

**7.** Maintain its therapeutic activity

**3.** Reduced dose size

**6.** Longer circulation time

SiO2

proliferation [75].

**2.** Easily changeable physical properties due to nanosizes

**Figure 3.** Representation of toxicological mechanisms of NM to eukaryotic cells.

#### **2.1. Inorganic nanoparticles**

Silver (Ag), iron oxide (Fe<sup>3</sup> O4 ), titanium oxide (TiO<sup>2</sup> ), copper oxide (CuO), and zinc oxide (ZnO) are used for highly potent antibacterial effect. The property is exhibited through reactive oxygen species (ROS) generation or by physical structure and metal-ion release. Though the mechanism is not clear, nonetheless high surface energy may compromise their efficacy. Another important aspect is that how to define and determine the silver minimal inhibitory concentration (MIC) and breaking point, the ease of emergence of resistant strains [81–83]. Silver really kills biofilm or planktonic cells and finally the side effects of silver and its complexes [84–87] remains the same. Yet till now it is the most promising antibacterial nanometal. Titanium oxide (TiO<sup>2</sup> ) has shown its efficiency against various viral species and parasites [88–90]. Copper oxide (CuO) is less expensive and used for efficacy enhancement [91–93]. Iron oxide (Fe<sup>3</sup> O4 ) [94], zinc oxide (ZnO) and Magnesium oxide (MgO) [95–97] nanoparticles show antibacterial activities. Gold nanoparticles and nanorods have been used as bactericidal in photothermally functionalized form [98]. Pt nanoparticles diffuse through membranes and induce DNA damage, accumulation of cells at the S-phase of the cell cycle, and apoptosis [99]. The properties of Al2 O3 are unclear about the antibacterial treatment [100], while SiO2 , Au, Fe2 O3 , and TiO2 are biocompatible.

Even cytotoxic NM can be converted into biocompatible materials through slight variation in their surface structure. Therefore, we can say that nanomaterials possess a broad level of biological properties that are highly dependent upon their size, structure, quantity, and receptor cell type. Though, the nanomaterials that penetrate the body through the skin by respiration or by inhalation directly affect the major body organs (lungs, heart, and brain).

#### **2.2. Organic nanoparticles**

Quaternary ammonium compounds, imidazole derivatives, alkyl pyridiniums, copolymers of N-vinylimidazole and phenacyl methacrylate, benzoic acid, phenol, and p-Hydroxy benzoate esters, quaternary phosphonium or sulfonium groups, triclosan, 5-chloro-8-hydroxy-quinoline, chitosan, or quaternary phosphonium are the polymeric nanoparticles that are used to kill microorganisms either by releasing antibiotics, antimicrobial peptides, and antimicrobial agents or by contact-killing cationic surfaces. Organic antibacterial materials are less stable than inorganic materials at high temperatures [101, 102]. Still some phenomena such as several NM killing pathways, effects of NM's treatment combinations and bacterial intrinsic pathways of programmed cell death in NM's dependent killing are yet to be understood.

As we all know, hepatocellular carcinoma (HCC) is the leading cause of cancer-associated death and the conventional treatment is still not satisfactory due to chemoresistance and recurrence. In a recent study, Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters was synthesized incorporating a pH-sensitive polymer and HCC-targeting peptide [103] .

The advantage of Pt nanocluster medicine is that Pt-NA is active in peripheral blood and readily targets tumor cells including CLSC because of (i) the surface-targeting peptide; (ii) protonation of pH-sensitive polymers in an acidic intracellular environment triggers Pt-NA disassembly into extremely small Pt nanoclusters; and (iii) the resulting extremely small Pt nanoclusters with large specific surface accelerate the release of toxic Pt ions inside the cells for an effective cancer treatment (**Figure 4**).

**2.1. Inorganic nanoparticles**

10 Recent Progress in Organometallic Chemistry

Silver (Ag), iron oxide (Fe<sup>3</sup>

nanometal. Titanium oxide (TiO<sup>2</sup>

and apoptosis [99]. The properties of Al2

O3

[91–93]. Iron oxide (Fe<sup>3</sup>

, Au, Fe2

**2.2. Organic nanoparticles**

while SiO2

O4

O4

), titanium oxide (TiO<sup>2</sup>

(ZnO) are used for highly potent antibacterial effect. The property is exhibited through reactive oxygen species (ROS) generation or by physical structure and metal-ion release. Though the mechanism is not clear, nonetheless high surface energy may compromise their efficacy. Another important aspect is that how to define and determine the silver minimal inhibitory concentration (MIC) and breaking point, the ease of emergence of resistant strains [81–83]. Silver really kills biofilm or planktonic cells and finally the side effects of silver and its complexes [84–87] remains the same. Yet till now it is the most promising antibacterial

parasites [88–90]. Copper oxide (CuO) is less expensive and used for efficacy enhancement

nanoparticles show antibacterial activities. Gold nanoparticles and nanorods have been used as bactericidal in photothermally functionalized form [98]. Pt nanoparticles diffuse through membranes and induce DNA damage, accumulation of cells at the S-phase of the cell cycle,

Even cytotoxic NM can be converted into biocompatible materials through slight variation in their surface structure. Therefore, we can say that nanomaterials possess a broad level of biological properties that are highly dependent upon their size, structure, quantity, and receptor cell type. Though, the nanomaterials that penetrate the body through the skin by respiration or by inhalation directly affect the major body organs (lungs, heart, and brain).

Quaternary ammonium compounds, imidazole derivatives, alkyl pyridiniums, copolymers of N-vinylimidazole and phenacyl methacrylate, benzoic acid, phenol, and p-Hydroxy benzoate esters, quaternary phosphonium or sulfonium groups, triclosan, 5-chloro-8-hydroxy-quinoline, chitosan, or quaternary phosphonium are the polymeric nanoparticles that are used to kill microorganisms either by releasing antibiotics, antimicrobial peptides, and antimicrobial agents or by contact-killing cationic surfaces. Organic antibacterial materials are less stable than inorganic materials at high temperatures [101, 102]. Still some phenomena such as several NM killing pathways, effects of NM's treatment combinations and bacterial intrinsic pathways of programmed cell death in NM's dependent killing are yet to be understood.

As we all know, hepatocellular carcinoma (HCC) is the leading cause of cancer-associated death and the conventional treatment is still not satisfactory due to chemoresistance and recurrence. In a recent study, Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters was synthesized incorporating a pH-sensitive polymer and HCC-targeting peptide [103] . The advantage of Pt nanocluster medicine is that Pt-NA is active in peripheral blood and readily targets tumor cells including CLSC because of (i) the surface-targeting peptide; (ii) protonation of pH-sensitive polymers in an acidic intracellular environment triggers Pt-NA disassembly into extremely small Pt nanoclusters; and (iii) the resulting extremely small Pt

O3

, and TiO2 are biocompatible.

), copper oxide (CuO), and zinc oxide

) has shown its efficiency against various viral species and

are unclear about the antibacterial treatment [100],

) [94], zinc oxide (ZnO) and Magnesium oxide (MgO) [95–97]

Numerous efforts have been devoted to synthesize nanostructured materials with specific morphology as their size and shape play an important role in determining their functions. It was seen that the cationic nanoparticles with metals (gold, silver, and cobalt) or metal oxides (Fe<sup>3</sup> O4 , TiO2 , and SiO2 ) were moderately toxic than their anionic nanoparticles. The studies reflect that DMSA coated nanoparticles are nontoxic to HeLa cells or RAW macrophages. The incorporation of chlorotoxin onto functionalized Fe<sup>3</sup> O4 nanoparticles resulted in a significant increase in the total uptake within the brain tumors of mice. Substituted magnetic spinel ferrites of the general formula MFe2 O4 (where M = Zn2+, Mn2+, Co2+, Ni2+, and Mg2+) offer the opportunity to fine-tune the magnetic properties of the inorganic nanoparticle core as a function of the kind of divalent ion.

**Figure 4.** Schematic representation of HCC targeted Pt nanocluster assembly (Pt-NA). Adapted with permission from American Chemical Society [103].
