The Prefix Nano Means A Billionth

Published Date: 02 Nov 2017

1.1 Introduction

The prefix "nano" means a billionth (1×10−9) of any unit of measurement. Any functional material having its size or at least one dimension in a billionth of a meter is termed as a nanostructured material or a nanomaterial. The use of these nanomaterials in the manufacture of useful devices and machines is known as nanotechnology.

The ideas and concepts behind nanoscience and nanotechnology started with a talk entitled "There’s Plenty of Room at the Bottom" by physicist Richard Feynman at an American Physical Society meeting at the California Institute of Technology (CalTech) on December 29, 1959. In his talk, Feynman described a process in which scientists would be able to manipulate and control individual atoms and molecules. But it wasn't until 1981, with the development of the scanning tunneling microscope that could "see" individual atoms that modern nanotechnology began. However it remains a fact that functional devices and structures of nanometer dimensions were not new to mankind. For example, in fourth-century A. D. Roman glass makers were fabricating glasses containing nanometer size metals. Artifacts from that period, the Lycurgus cups, which contain metal nanoparticles, reside in the British Museum in London. Medicinal preparation called Bhasma used in the traditional Ayurvedic system of healing that originated in India even before 800 AD contain nanoparticles [1]. However, a taxonomical study of these structures for potential application is relatively new.

Nanostructured materials compose a bridge between molecules and infinite bulk systems [2]. Hence they are obeying neither absolute quantum chemistry nor laws of classical physics and have properties that differ markedly from those expected from the bulk materials. Because of their ultra fine size, high surface area and useful interfacial defects [3-5] nanomaterials demonstrate superior chemical, biological, mechanical, electronic, magnetic, and optical properties that are often drastically different from their subsequent micro counterpart [6]. Research on nanomaterials is highly interdisciplinary because it requires synthetic skills and characterization proficiency. Synthesis of nanomaterials plays a significant role for cutting edge applications, and revolves around the issue of assembling atoms or molecules into nanostructures of the desired coordination environment, size, and shape. [5].

Fig.1: Schematic representation of the ‘bottom up’ and top down’ approch

Nanostructured materials can be synthesised using "bottom-up [7] and top-down [8] techniques" (Fig.1). These two approaches for synthesis again point towards the fact that nanostructured materials are an intermediate state between individual atoms and bulk materials. The properties of these materials are different from parent atom or bulk materials. Bottom-up approach refers to the buildup of a material from the bottom: atom by atom, molecule by molecule or cluster by cluster; this approach is used for molecular synthesis, colloid chemistry and polymer science. Top-down approach involves successive cutting of a bulk material to get nanosized particle; it includes high- energy milling, ion implantation, lithography, laser ablation, sputtering, vapor condensation, and etc. Engineers generally adopt top-down strategy; by starting from well-established structures of the macro-world they venture into nanometer range via consecutive cycles of miniaturization. In contrast, chemists generally use a bottom-up approach as they synthesize simple compounds consisting of just a few atoms and then extend them into long macromolecules.

The bottom-up approach makes use of chemical or physical forces operating at the nanoscale to collect fundamental units into larger structures. Nature has many objects and processes which adopt the self activated bottom-up approach, such as amino acids, monosaccharide or lipid in order to create a wide range of complex structures needed by life [9]. In that way, researchers tried to imitate this ability of nature. The main advantage of the bottom-up approach is that there are a wide variety of preparation methods available which allow good control on the scale dimension, furthermore they are not as expensive as top-down approaches.

Chemical precipitation is one of the basic bottom-up techniques used to fabricate nanomaterials. This method allows producing nanoparticles of metals, alloys, oxides, etc. from aqueous or organic solutions following relatively simple and cost-effective steps. But the method has the least ability to control the particle size distribution; hence this method is not frequently used for nanoparticles synthesis. Other bottom-up methods that give more control on the size of the nanoparticles during synthesis include microemulsion, thermal decomposition, sol-gel, microwave assisted method etc. These chemical methods that give uniform and stable nanoparticles are reviewed below:

1.2 Synthesis of nanostructured materials

1.2.1 Microemulsion

Microemulsions or reverse micelles can provide an attractive micro reactor for preparing nanoparticles, where the morphology of nanoparticles can be well controlled. Microemulsions consist of a ternary mixture of water, a surfactant and oil. This method is based on the solubility enhancement of organic compound in aqueous phase (oil-in-water (o/w) emulsion) or hydrophilic compound in the oil phase (water-in-oil (w/o) emulsion). This process has been used for the synthesis of various nanoparticles by mixing two micro-emulsions containing appropriate reactants. With this method, it is possible to synthesize and/or align a wide range of nanomaterials. Gold and silver nanoparticles and bimetallic nanoparticles have been prepared by several microemulsion methods; with the use of, 4-bis (2-ethylhexoxy)-1, 4-dioxobutane-2-sulfonate (AOT) [10-12]. Cu NPs are obtained by the reduction of a micellar solution of Cu(DS)2 (DS, dodecyl sulfate) with NaBH4 [13]. In addition monodispersed metal oxide, metal sulphide and alloy nanoparticles were also synthesized by this method [14].

1.2.2 Thermal decomposition

Thermal decomposition technique is used to synthesize inorganic metal nanoparticles. Metal NPs are generated by the thermal decomposition of molecules containing zero-valent metals, such as metal carbonyls. [15] In this method organometallic precursor compounds and surfactant are heated up to the combustion temperature of the metallic salt. Synthesis of metal oxide nanoparticles by combustion synthesis is well documented [16] Pd nanoparticles were prepared by the thermal decomposition of Pd–trioctylphosphine (TOP) complex at 300 °C for 30 min [17]. Co nanoparticles can be synthesized by a high-temperature thermal decomposition of Co2 (CO) 8 in the presence of oleic acid (OA) and triphenylphosphine at 220 °C [18]. Bimetallic FePt and CoPt nanoparticles were obtained by reacting Pt(acac)2with 1,2-hexadecanediol (HDD) and trioctylphosphine oxide (TOPO) at 100 °C followed by the addition of Fe(CO)5 or Co2 (CO)8 at 286 °C for 30 min respectively [19]. Furthermore, metal oxides such as iron oxide, copper oxide and metal phosphors (GaP, InP, Fe2P) nanoparticles have also been synthesized by this methods [20-22].

1.2.3 Sol-gel Method

The sol–gel process in general is based on the transition of a system from a liquid "sol" (mostly a colloidal suspension of particles) into a gelatinous network "gel" phase. The sol–gel method is generally employed for the synthesis of metal oxide NPs as well as oxide nanocomposites. The sol–gel process involves the hydrolysis and condensation of metal precursors [23]. The sol–gel process can be either in aqueous or non-aqueous medium. In the aqueous sol–gel process, oxygen for the formation of the oxide is supplied by water molecules. In the non-aqueous process, oxygen is provided by a solvent (ethers,alcohols, ketones, or aldehydes) or by an organic element of the precursor (alkoxides or acetylacetonates)[24].

In sol-gel process the "sol" is prepared by mechanically mixing of liquid alkoxide precursor (such as tetramethoxysilane, TMOS, or tetraethoxysilane, TEOS), water, a co-solvent, and an acid or base catalyst at room temperature. During this step, the alkoxide groups are removed by the acid- or base-catalyzed hydrolysis reactions, and networks of O–M–O linkages are formed in subsequent condensation reactions.

After this step, the treatment of the sol is varied depending on the final products desired. For example, spinning or dipping techniques can create thin film coating, and the exposure of the sol to a surfactant can lead to powders.

Depending on the water–alkoxide molar ratio R, the pH, the temperature, and the type of solvent chosen, additional condensation steps can lead to different polymeric structures, such as linear, entangled chains, clusters, and colloidal particles. In some cases, the resulting sol is cast into a mold and dried to remove the solvent. This leads to the formation of a solid structure in the shape of the mold (e.g., aerogels and xerogels) with large surface-to-volume ratios, high pore connectivity, and narrow pore size distribution. They can be doped with a variety of organic/inorganic materials during the mixing stage to target specific applications. Various metal oxides such as ZnO, ZrO2, iron oxide, CeO2, and ferrites have been synthesized by a sol–gel method.

1.3 Classification of Nanoparticles

Using the various synthetic procedures discussed above a large number of nanoparticles has been reported with various applications in the fields of sensor technology, therapeutics, optical and electronic devices, etc. These nanomaterials can be broadly classified based on their constitution as: Inorganic, Polymer-based nanoparticles, Hybrid materials etc.

In the present work we have focused on some inorganic nanomaterials and polymer based nanomaterials. These two types of nanoparticles, their properties and applications are discussed below.

Inorganic nanoparticles

Inorganic particles have frequently demonstrated novel physical properties when their size is in nanometer scale dimensions. Inorganic nanoparticles like noble metals, metal oxides, magnetic, and semiconductor nanocrystals (quantum dots), are emerging as a novel class of nanomaterials having varied applications.

Semiconductor nanoparticles with sizes between ~1 and 10 nm have received much attention since the early 1980s. They are generally referred to as quantum dots and due to their unique electronic and optical properties they may have future applications in various fields such as electro optic devices and biomedical imaging [25].

The noble metals nanoparticles (Cu, Ag and Au) exhibit physical properties that make them unique for scientific and technological applications: electronics, catalysis, biotechnology, spectroscopy, etc. They are relatively easy to synthesize and have been investigated thoroughly for their unique properties.

Metal oxides like iron oxide nanoparticles, are currently under investigation because of their magnetic properties which make them potentially useful as contrast agents for molecular resonance imaging (MRI) [26]. Iron oxide nanoparticles are also capable of being manipulated under an external magnetic field, [27] it is also used as an effective hyperthermia agent for cancer treatment. [28]

The types of inorganic nanoparticles and the specific ones chosen for the present work have been discussed in detail below.

1.3.1 Semiconductor nanostructured materials

Semiconductors are the materials whose electrical resistivity lies between 10 −2 to 109 Ω cm at room temperature. The band gap of these materials falls between 0 to 4 eV and this group of materials show many commonality in their physical properties. There are a large number of materials showing semiconducting behavior. In periodic table; group II, III, IV and V contain elements with semiconductor properties. Among them group IV elements are exceptional in the sense that the outer orbital of an individual atom is exactly half filled. So each atom can complete its outer shell by sharing electrons with four other atoms of the same kind through covalent bonds. Hence group IV elements can only crystallize in diamond structure in the whole periodic table. The group II atoms can make covalent bond with group VI atoms and group III atoms with group V atoms. These materials are termed as II-VI or III-V compound semiconductors.

Nanostructures of these semiconductors especially the II—VI group show extensive and novel applications due to their unique properties and straightforward as well as varied synthetic procedures [29]. Wide band-gap of II—VI semiconductors have been intensively studied for many years due to their great potential for a variety of applications, in particular in the areas of electronic devices, phosphor, light-emitting and light-detecting devices, photo-voltaic conversion (solar cells), X-ray detection etc.. II—VI compounds are also promising materials for optoelectronic applications, in particular for fabricating short-wavelength light-emitting diodes (LEDs) and laser diodes (LDs). Based on the achievement of p-type conduction via plasma-activated nitrogen doping, the first blue-green LD was developed from ZnSe in 1991[30], which was about five years earlier than the report of the first GaN-based blue LD in 1996[31]. Owing to their high sensitivity and high quantum efficiency, II—VI photodetectors are ideally suited for light detection ranging from near infrared to ultraviolet, e.g., CdTe and ZnTe, have shown more attractive potentials in nuclear radiation detection at room temperature.

There are still more examples to illustrate the potentials of II—VI semiconductors in a variety of significant applications. Nevertheless, some application areas such as electronic and optoelectronic applications require still higher quality II—VI semiconductors with controlled defects and impurities. Therefore, the obtainment of device-quality and single-crystal II—VI semiconductor bulks/films is essential. The advances in nanoscience and nanotechnology open new opportunity for the application of II—VI semiconductor materials.

Zinc sulfide (ZnS), an important member of II-VI group semiconductor materials, is having great interest for its practical applications in optoelectronics and photonics [32-35]. Because of its wide bandgap (3.73 eV), it has a high index of reflection and a high transmittance in the visible range, particularly suitable for host material for a large variety of dopants. It has been extensively studied for a variety of applications like optical coatings, field effect transistors, optical sensors, electroluminescence, phosphors, and other light emitting materials [36-37].

Many research works have been carried out on this material at nanoscale [38]. A variety of methods have been reported for the preparation of nano-ZnS. These methods include soft solution synthesis, sol-gel synthesis, chemical vapor deposition, hydrothermal conditions, microwave irradiation, and so forth [38]. These novel routes for synthesis of optoelectronic materials are an integral aspect of material chemistry and physics. The colloidal synthesis route is another novel method of synthesis and is a developing area in the field of research. In this technique, concentration of reagent, capping agent to precursor ratio, pH, time, and temperature play important role to control the morphology and size of the ZnS nanoparticle.

Synthesis of ZnS nanostructures

ZnS nanostructures have attracted significant interest due to their transfixing properties, as well property–microstructure correlation. They can be divided into three kinds, namely 0, 1, and 2 dimensional (D) nanostructures based on their shapes.

0D ZnS nanostructures

In the past few years, significant development has been made in the field of 0D nanomaterials and nanostructures. In the beginning, Brus et al. successfully synthesized ZnS nanocrystals with high colloidal stability in aqueous and methanolic media using Na2S and Zn(ClO4)2as precursors but the nanocrystals were not monodisperse [39]. This limitation of size tunability was moved out by ground-breaking non-hydrolytic method which was previously used for the synthesis of monodispersed CdSe nanocrystals. Hyeon et al. fabricated cubic ZnS nanocrystals with various sizes and shapes under a thermal reaction of ZnCl2 and S in oleylamine in the presence of TOPO. Polyol method is also an useful process to synthesize uniform nanocrystals. Zhaoet al. synthesized hexagonal ZnS nanocrystals at temperatures as low as 150ºC using ZnCl2and S as precursors in a polyol medium [40]. These ZnS nanocrystals are quite uniform in both shape and size. An average size is 4.2 nm with a standard deviation of 0.6 nm.

1D ZnS nanostructure

1D nanostructure has stimulated an increasing interest due to their importance in basic scientific research and potential technological applications [41]. These nanostructures play an important role as both interconnects and the key units in fabricating electronic, optoelectronic, electrochemical, and electromechanical devices with nanoscale dimensions [42-43]. Various kinds of 1D ZnS nanostructures have been reported in the literature. X.S. Fang and co-workers synthesized a variety of ZnS containing 1D nanostructure, such as nanowires, nanobelts, nanotubes, nanocombs, nanowalls (Fig.2) [44].

Fig.2: Several typical morphologies of ZnS-related 1D nanostructure. Reproduced from Ref. [44]

Yin et al. fabricated ZnS nanotubes by a high-temperature thermal chemical reaction route, in which commercial ZnS powders were used as precursors and H2O vapor was carried by Ar gas and introduced into a graphite crucible to form reductive agents of CO and H2[45].

2D ZnS nanostructures

ZnS thin films have been fabricated by several techniques, such as vacuum deposition, metal–organic chemical vapor deposition (MOCVD), molecular beam epitaxy (MBE), spray pyrolysis, chemical bath deposition (CBD), sol–gel, and chemical vapor deposition. Herrero et al. synthesized ZnS films by CBD with a decent growth rate using NH2–NH2 as a complementary complexing agent for the classically used NH3 reaction baths. The ZnS film consisted of small granular particles (~1µm in diameter), and the grain sizes were about 10 times smaller than those in the thermally-produced films [46].

Applications of ZnS nanostructures as a chemical and biomolecule sensors

Semiconductor nanocrystals (NCs) have a very good photostability, continuous absorption spectra, efficient, narrow, and tunable emission, which have been widely exploited for applications in biological imaging and in single particle tracking studies. Due to the small size and unique optical properties of ZnS nanoparticles it becomes an excellent sensing material. In addition, ZnS nanostructures are very suitable for applications in biological fields due to less toxicity among other II–VI semiconductor nanoparticles. In recent years many ionic and bimolecule sensors have been reported which are based on the unique optical property of ZnS nanostructures.

Nian Bing Li co-workers fabricated a cetyltrimethylammonium bromide-capped Mn-doped ZnS quantum dots for the room-temperature phosphorescence (RTP) detection of mercury ions [47]. In addition Xinyong Li et al. made cadmium-free ZnSe/ZnS quantum dot-based chemosensor for sensitive detection of Hg2+ ions. This nanosensor takes advantage of the metal-induced aggregation strategy for selectively and rapidly detection of Hg 2+ions on the nanomole scale in aqueous solution [48]. Copper (Cu) is one of the common metals and essential elements for many living organisms, and also becomes toxic at high levels. Cu2+ ions are detected by various set up of ZnS nanostructures; silica-coated ZnS:Mn nanoparticles and l-cysteine-capped ZnS QDs are sensitive sensor for Cu2+ ions [49]. Cysteine is a water-soluble amino acid and used as a capping agent for ZnS QDs. The surface modification of ZnS QDs with cysteine prevents the aggregation of nanoparticles and makes them available for the interaction with the target materials. Goutam De et al. synthesized magic sized ZnS quantum dots by simple green chemistry from Zn-acetate, sodium sulfide and thiolactic acid (TLA) at room temperature in aqueous solution. Further these ZnS quantum dots act as a sensitive and selective fluorescence probe for Ag+ ions [50].

A biosensor is a device for the detection of an analyte that combines a biological component with a physicochemical detector component. Recently, Mulchandani et al. fabricated ZnS nanocrystals decorated single-walled carbon nanotubes which act as a chemiresistive sensor for DNA [51]. 3-Mercaptopropionic acid- capped Mn- or Cu-doped ZnS quantum dots can be used as novel fluorescence nanosensors for folic acid in aqueous medium. The fluorescence sensor for folic acid is based on the fluorescence quenching of the doped ZnS quantum dots [52]. Sodium thioglycolate modified ZnS nanoparticles have been reported as a fluorescence probe of proteins further this probe gives its application in real biological samples also [53]. On other hand P S Negi et al. used unmodified ZnS nanoparticles for the selective detection of adenine. The amino (–NH2) group in adenine plays an important role in the quenching of the ZnS luminescence [54].

From past few years; there is increasing interest in the host–guest chemistry on the surface of quantum dots (QDs) and in the changes that it produces in the luminescent properties of QDs. In this chemistry "host" molecules, containing a binding site that is highly specific for an analyte "guest," are used as sensors to register analyte binding through a variety of mechanisms such as colorimetric, fluorescent, or electrochemical signals. ZnS nanostructures containing supramolecular assembly are decidedly a striking probe for detection of some hazardous ions and bio and organic molecules. Haibing Li and co-workers fabricated a calixarene capped stable CdSe/ZnS core/shell quantum dots (QDs) for the selective determination of mercury ions in acetonitrile with high sensitivity [55]. By taking the advantage of the ability of the potassium cation to form a sandwich complex with two 15-crown-5 molecules; Chiu H et al. developed a 15-crown-5-modified CdSe/ZnS QDs sensor for sensitive detection of potassium cations in aqueous solution.

Amphiphilic calixarene derivatives have been used as a capping ligand for QDs, giving rise to water-soluble QDs. The use of p-sulfonatocalix[4]arene-coated CdSe/ZnS QDs was reported for the detection of acetylcholine based on the fluorescence quenching observed after binding the ammonium cation of the acetylcholine with the calixarene (Fig.3a) [56].

Fig.3 (a,b): Host–guest chemistry on the surface of QDs used for analyte sensing. . Reproduced from Ref. [56.57]

Simonet and co-workers reported an optical sensor for fullerene C60 in water using CdSe/ZnS quantum dots coated by p-tertbutylcalix[8]arene (Fig.3b). This C60-nanosensor is based on the selective host-guest interaction between fullerene C60 and p-tertbutylcalix[8]arene.[57]

1.3.2 Metal nanoparticles

Noble metal nanoparticles are of valuable technological importance because of their unique physiochemical properties and applications in the fields of catalysis, information storage, optoelectronics, sensors, fine chemicals synthesis, oil refining processes, and fuel cell technology. Hence much attention has been paid in recent years to develop methods of synthesizing monodispersed noble metal nanoparticles like Pt, Rh, Pd, Ir, Au, and Ag [58].

Gold nanoparticles

Gold nanoparticles (GNPs) are the most widely investigated among all other nanoparticles due to their unique tunable optical properties, which can be applied in various applications such as sensing, detecting, and imaging. GNPs represent an excellent nano-platform in developing analytical methods for biosensing and many research groups have demonstrated a wide range of sensing applications, for chemical to biological samples [59-60].

In recent age the application of gold nanoparticles is not limited to sensor technology but it is also an attractive candidate for photothermal therapeutics, diagnostics, and drug and gene delivery applications [61-62]. GNPs show unique physicochemical properties including surface plasmon resonance (SPR) and the ability to bind amine and thiol groups, allowing surface modification and use in biomedical applications [63]. Functionalization of GNPs is a subject of intense research, with rapid progress being made towards the development of biocompatible, multifunctional particles for use in cancer diagnosis and therapy. Properly functionalized GNPs not only can serve as a drug reservoir, but also provide a long circulation time and low cytotoxicity; thus, they have emerged as attractive candidates for delivering various small drug molecules into their targets [64-66]. There are various approaches for using gold nanoparticles as a drug delivery vehicle, including systems based on covalent binding, drug encapsulation [67-70], electro-static adsorption [71], and other non-covalent assemblies [72].

Synthesis of gold nanoparticles

Gold nanoparticles can be prepared very easily by the reduction of diluted aqueous solutions of HAuCl4 with citric acid or trisodium citrate respectively. If trisodium citrate is used, a very narrow size distribution is observed with standard deviations of only 10%. Variation of the experimental conditions allows the synthesis of particles with diameters between 14 and 900 nm. Wang and coworkers established the synthesis of smaller gold nanorods (ca.10 nm in diameter) by electrochemical oxidation of a gold plated electrode in the presence of cationic, quaternary ammonium surfactants (cetyltrimethylammonium bromide, or CTAB, and tetraoctylammonium bromide, or TOAB) and under ultra-sonication. However, when the size of nanoparticles becomes larger than 50 nm, the monodispersity and the shape will be disrupted. Many research groups have tried different reducing agents with sodium citrate. For example, Perrault and co-worker recently demonstrated the use of hydroquinone as reducing agent and successfully produced GNPs[73] In recent years, many research groups have made significant effort in developing new synthetic methods for making different size and shape of GNPs with various combinations of reducing and capping agents. More recently, Aslam and co workers [74] have demonstrated a one-step process for the making of water-dispersible GNPs using the oleylamine as both reducing and capping agents. Kim et al. [75] reported a one-phase synthesis of GNPs using thiol-functionalized ionic liquids. In this case the authors hypothesize that the NP size and distribution depend on the number and position of thiol groups in the ionic liquids. GNPs were also synthesized by use of salicylic acid and polyethylene glycol.

Recently green synthesis approaches have also been reported for making GNPs. Many biomolecules act as a reducing as well as stabilizing agents and form GNPs. For example, polysaccharides and biopolymers generally are used as both Stabilizers and reducing agents to synthesize GNPs. P. Raveendran et al. have used starch as a stabilizer and glucose as a reducing agent for GNPs formation [76]. Recently, Zhaowu Zhang et al. fabricated folic acid-protected gold nanoparticles by one-step reduction of HAuCl4 with folic acid [77].

Application of gold nanoparticles in Cancer treatment

Gold nanoparticles easily conjugate with a variety of bio-functional molecules by simple physical methods such as hydrophobic–hydrophobic interaction and charge-pairing. This property makes them an effective drug carrier for targeted drug delivery. GNPs are nontoxic carriers for drug and gene delivery applications [78]. Several types of therapeutic agents such as proteins, peptides, nucleic acids, and small- molecule of drugs have been conjugated to GNPs to form GNPs-based nanodrugs[79].

Fig.4: Various applications of GNps in cancer treatment Reproduced from Ref.[79]

For the targeted drug delivery GNPs first conjugate with targeting moieties; monoclonal antibodies (mAbs), antibody fragments, peptides, proteins, aptamers etc. used as targeting moieties [80]. In addition, peptides are also becoming attractive targeting molecules because of their high specificity, high affinity, high stability, and easy preparation. Some tumor-domiciliating peptides, which are targeted specifically to tumor blood vessels, lymphatic vessels and/or tumor cells, have been isolated [81-82]. The use of these peptides as targeting moieties, increased intracellular drug delivery in different murine tumor models [82]. Proteins, including human serum albumin (HSA), transferrin and lectins, have been used as targeting moieties, drug-delivery systems, or both [83-84]. Though, reflection of their receptors or targets is not limited to tumor tissues, which may pose harm to normal tissues. Small molecules such as folic acid and biotin have shown great potential as a class of targeting molecules because of their small size and low cost of fabrication [85-87]

A variety of therapeutic approaches have been developed which take advantage of the well-researched covalent chemistry of gold nanoparticles. GNPs covalently coupled with anticancer drugs and made GNPs-drug conjugates. After conjugation with GNPs many anticancer drug such as cisplatin, paclitaxel, tamoxifen, and doxorubicin shows effective anticancer activity compared to free drugs. This is useful, but must eventually be combined with increased specificity of the drug conjugate to cancer cells.

Recently, Nial J. Wheate et al. [88] have synthesized platinum-tethered gold nanoparticles for targeted drug delivery. The effectiveness of platinum-based anticancer drugs such as "cisplatin, carboplatin, and oxaliplatin" can be improved through the use of drug-delivery vehicles that are able to target cancers passively or actively. In this work the authors functionalized GNPs by thiolated poly(ethylene glycol) (PEG) and then [Pt(1R,2R-diaminocyclohexane)(H2O)2]2NO3 was added to the PEG surface. The platinum-attached nanoparticles demonstrated significantly better, cytotoxicity than oxaliplatin alone in the lung cancer cells.

Recently, Mirkin et al. have synthesized oligonucleotide–gold nanoparticle conjugates with paclitaxel in order to increase its solubility in aqueous media [89]. Paclitaxel, which is highly insoluble in water, was solubilized by attaching to the gold nanoparticles, including in high-salt buffers. The gold nanoparticle–DNA–paclitaxel conjugates were shown to be internalized by the cells and showed increased cytotoxicity compared to free paclitaxel. El-Sayed and coworkers reported the first example of covalent coupling of tamoxifen to gold nanoparticles by attaching it to a thiolated PEG linker [90].

Another interesting example of anticancer drug that has been conjugated to gold nanoparticles is 5-fluorouracil, a drug which inhibits DNA and RNA synthesis. Agasti et al. synthesized fluorouracil-functionalized gold nanoparticles of 2 nm size [91]. Irradiation of these nanoparticles with 365 nm UV light resulted in controllable release of the drug, which exerted its cytotoxic effect only when it was released from the particle surface.

In recent times, gold nanoparticles have been covalently grafted with doxorubicin for treatment of drug-resistant breast cancer [92]. Doxorubicin was attached through a thioctic acid-PEG linker to the surface of 30 nm citrate-capped gold nanorods through a hydrazone group.

1.3.3 Metal oxide and carbonate particles

Metal oxide and metal carbonate nanoparticles exhibit unique properties in regard to sorption behaviors, magnetic activity, chemical reduction, and bactericides. Due to these properties they have many applications in various fields such as; separation, catalysis, environmental remediation, sensing, biomedical and others. [93-94]. Nano-sized metal oxide particles, such as metal oxides of zinc, copper, and iron are being generated for critical use in medical practices, in biomedical research [95] because of their ability to inhibit bacterial growth population by specific nanoparticle interactions in the growth medium. It has been demonstrated that TiO2 nanoparticles embedded in a hybrid organic/inorganic membrane can have bactericidal activity under UV-light illumination [96]. CuO nanoparticles were effective in killing a range of bacterial pathogens involved in hospital-acquired infections [97].ZnO nanoparticles could potentially be used as an effective antibacterial agent to protect agricultural and food safety from food borne pathogens, especially E. coli O157:H7 in culture media [98-99].

MgO nanoparticles are a functional material that has been widely used in various areas. Recently, it has been reported that MgO nanoparticles has a good bactericidal performance in aqueous environments due to the formation of superoxide (O2-) anions on its surface [100-101]. Klabunde and co-workers [102] demonstrated that nano- MgO exhibits high activity against bacteria, spores and viruses after adsorption of halogen gases because of its large surface area, copiousness in crystal defects and positively-charged particles which can result in strong interactions with negatively-charged bacteria and spores [103] Activity of such nanoparticles in part depends on size and stability of nanoparticles. However, metal oxide nanoparticles have modest chemical stability and mechanical strength which limits its excellent antibacterial properties. This limitation can be overcome by appropriately dispersing metal and metal oxide nanoparticles into synthetic and naturally occurring polymers. Polymer-supported metal or metal oxide nanoparticles are a new class of hybrid polymeric/inorganic materials that lead to the enhancement of the properties of nanoparticles. The dispersion of metal or metal oxides inside the host material can take place through a combination of different mechanisms such as complexation/chelation, electrostatic interactions, precipitation or reduction reactions, etc. The synthesis of hybrid materials involves two broad pathways: dispersing the nanoparticles (i) within pre-formed or commercially available polymers (ex-situ); and (ii) during the polymerization (in-situ) process [104].

The ex-situ process consists of physical entrapment of the metal or metal oxides nanoparticles in the polymer or biopolymer network through casting and solvent evaporation, chemical polymerization, or co-precipitation. Such encapsulation of nanoparticles also helps in the stabilization of nanoparticles by preventing them to agglomerate and form larger particles. In contrast, during in-situ process the nanoparticles of metal and metal oxides are synthesized within a pre-formed polymer frame-work or matrix.

The practical applications of metal oxide-polymer nanocomposites cover wide fields because the composites combine the properties of the nanoparticles and polymers. Brown et al [105] described the encapsulation of Fe2O3 in alginate matrix for the drug delivery of magnetic-resonance imaging contrast agent and for hyperthermic treatment of malignant tumors. Ma et al. [106] reported a series of applications of super paramagnetic iron oxide nanoparticles immobilized in alginate in the field of health.

Polymer–metal oxide nanocomposites can also find application for disinfection in water treatment. The nanoparticles are captured inside a polymer matrix that confine the bacteria and prevents their escape into the water.

Recently, metal oxide-polymer nanocomposites have been reported as antibacterial agents [107-108]. Metal oxide nanoparticles have been widely used in cosmetics, sunscreens, toothpaste, etc. In all these field of application, nanoparticles are placed directly on the skin and penetrate dermal tissues [109] and skin fibroblasts. In metal oxide-polymer nanocomposites; polymer matrix prevents direct interaction between metal oxide nanoparticles and formative cell it helps to reduce toxic effect of bare metal oxide nanoparticles.

Metal carbonates have been intensively investigated in recent years because of their large quantity in nature and also their important industrial applications in paints, plastics, rubber, and paper. Moreover, the metal carbonates (e.g., CoCO3and MnCO3) are often used as solid precursors to synthesize their respective nanostructured metal oxides through chemical/ thermal conversion [110-111].

Metal carbonates such as barium carbonate (BaCO3) and strontium carbonate are an important material in industry to produce their respective salts, pigment, optical glass, ceramic, electric condensers. In addition, strontium carbonate has only one crystal-phase, so it has been widely studied as a model system for bio-crystallization. MgCO3 has been already reported to be an important additive as it has potential applications in plastics, as a dopant and in printing inks. In addition, it is also an attractive sorbent and intermediate for treating wastewater contaminated with dye and heavy metal ions [112]. Compared with traditional materials, nano-materials have shown much higher efficiency and versatile applications due to their size and surface effect. So, there has been extensive attention in fabrication of low-dimensional nanosized materials.

Xu et al. [113] synthesized BaCO3 nanowires in the Triton X-100/cyclohexane/water reverse micelles. Reverse micelle or microemulsion (soft template) is increasingly used to prepare nanowires and nanorods. BaCO3 nanoparticles were also synthesized by microemulsion and flame spray pyrolysis (FSP) methods [114-115]. Sun et al. [116] synthesized single crystalline BaCO3 with different morphologies and sizes by a superficial and practicable approach in the presence of polyvinylpyrrolidone (PVP) as a stabilizing agent at room temperature.

CaCO3 is also an important mineral, nanoparticles of CaCO3 have been synthesized by various techniques; in recent times bacteria mediated CaCO3, nanoparticles were created by Long Chen et al [117]. Calcium carbonate nanoparticles were also prepared by carbonation and Wegner’s methods [118].

Metal carbonate nanoparticles act as outstanding water purification materials. Poly(acrylic acid) stabilized amorphous calcium carbonate nanoparticles can remove toxic heavy metal ions such as Cd2+ ,Pb2+ ,Cr 3+ ,Fe 3+ and Ni2+ from aqueous solutions [119]. Almost 65% of methyl blue was removed in 1h by porous and hallow Mg5(CO3)4(OH)2·4H2O nanorods[120]. In addition, CaCO3 nanoparticles exhibit good performance in anti-wear and friction-reduction, load-carrying capacity, and extreme pressure properties due to these mechanical engineering properties CaCO3 was used as an additive in lithium grease [121].  

1.4 Polymer-based nanoparticles

Polymeric nano and microparticles have recently been shown significant potential in drug delivery systems. Polymeric nanoparticles formulated from biodegradable polymers have been extensively investigated as carriers for controlled delivery of constructive remedies and biomolecules such proteins, peptides etc. [122-124]. Many researchers have shown that nano delivery systems can modify the biological distribution of drugs, proteins, and DNA, at the cellular and organ levels [125-127]

Furthermore, by transforming the polymer characteristics, one can control the release of a therapeutic agent from the nanoparticles to achieve a desired therapeutic efficacy at the target tissue for the required duration [128-129]. The commonly used biodegradable polymers are chitosan, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(e-caprolactone) (PCL), poly(hydroxybutyrate) (PHB) and their copolymers such as poly(lactide-co-glycolide) (PLGA). The copolymers have the advantage to maintain the release of the encapsulated curative agent over a period of days to several weeks. As polyesters in nature, PLGA undergo hydrolysis upon administration into the body, forming biologically compatible and metabolizable moieties (lactic acid and glycolic acid) that are ultimately removed from the body by the citric acid cycle.

PLGA nanoparticles have been mostly prepared by emulsification–diffusion, solvent emulsion–evaporation, interfacial deposition and nanoprecipitation method. Most commonly used method for the preparation of PLGA nanoparticles is nanoprecipitation. Polymers dissolved in acetone are added drop-wise into continuously stirring aqueous phase with or without emulsifier/stabilizer and consequently organic phase is evaporated under reduced pressure. In solvent evaporation method, the polymers are dissolved in volatile organic solvent and poured into continuously stirring aqueous phase with or without emulsifier/stabilizer and sonicated. Interfacial deposition methods have been used for the formation of both nanocapsule and nanospheres. The nanoparticles are synthesized in the interfacial layer of water and organic solvent (water miscible) and finally the nanoparticles are separated by centrifugation. In emulsification–diffusion method, the PLGA polymers are dissolved in organic solvent, poured and separated in stabilizer containing aqueous phase and consequently emulsified by homogenizer. PLGA has been approved by US Food and Drug Administration (USFDA) for human use and nanomedicines[130]. Many drugs such as paclitaxel, cisplatin, xanthones, dexamethasone, haloperidol have been successfully entrapped into/or adsorbed to PLGA nanoparticles. Biomolecules like insulin and some hormone are also encapsulated in to PLGA nanoparticles [131-135].

PLA (polylactic acid) polymer is biocompatible as well as biodegradable; it breaksdown in the body to monomeric units of lactic acid which is a natural intermediate in carbohydrate metabolism. PLA nanoparticles have been mostly prepared by solvent evaporation, solvent displacement, salting out and solvent diffusion. PLA nanoparticles encapsulated various drugs from various classes [136] and give excellent application as control and targeted drug delivery vehicles; it also encapsulates some biomolecules and prevents the early degradation of them [137-138].

PCL (poly-caprolactone) is degraded by hydrolysis of its ester linkages; it is especially interesting for the preparation of long-term implantable devices, because its degradation is slower than that of polylactide. PCL also incorporates small molecules such as tamoxifen, taxol, vinblastine and increases their therapeutic values [139-141].

The acidic nature of these synthetic biodegradable polymers is not suitable for some drugs or bioactive molecules [142-143]. To overcome these problems some natural biodegradable molecules such as chitosan, gelatin, poly (amino acid), and albumin are used as a nanocarriers for drug

Chitosan is a modified natural carbohydrate polymer prepared by the partial N-deacetylation of crustacean derived natural biopolymer chitin. There are at least four methods reported [144] for the preparation of chitosan nanoparticles as ionotropic gelation, microemulsion, emulsification solvent diffusion and polyelectrolyte complex [144]. Ionotropic gelation is renowned method it is based on electrostatic interaction between amine group of chitosan and negatively charged groups of polyanion such as tripolyphosphate[145-146]. In this method nanoparticles are spontaneously formed. In microemulsion method, a surfactant was dissolved in an organic solvent like n-hexane. Then chitosan in acetic acid solution and glutaraldehyde were added to surfactant/hexane mixture under continuous stirring at room temperature [147]. Chitosan nanoparticles can excellently encapsulate ammonium glycyrrhizinate[148] and improve the oral absorption of ammonium glycyrrhizinate. Glycyrrhetic acid inhibit progesterone metabolism either indirectly by preventing the regeneration of triphosphopyridine nucleotide or directly by inhibiting the reduction of progesterone. Moreover for the diabetes treatment insulin loaded chitosan nanoparticles are significantly more effective than insulin solution and physical mixture of oral insulin and empty nanoparticles [149]. Recently, much attention has been paid to chitosan as a drug carrier because chitosan has cationic characters even in neutral conditions to form complexes with negatively charged pDNA. Jeong et al. prepared deoxycholic acids modified chitosan nanoparticles which gives a prospective application as a gene delivery [150].

Gelatin is widely used in food and medical products and is attractive for use in controlled release due to its non-toxic, biodegradable, bioactive and inexpensive properties. Gelatin nanoparticles can be prepared by desolvation/coacervation or emulsion method. Many payloads have been successfully encapsulated into gelatin nanoparticles. Gelatin nanoparticles have been used for encapsulating bovine serum albumin and control the release profile of protein by diffusion-controlled mechanism. Furthermore gelatin nanoparticles become a decent carrier for some important drugs like paclitaxel, didanosine, chloroquine phosphate etc. [151-153].

Latterly, albumin-based nanoparticle carrier systems represent a striking strategy, since a significant amount of drug can be incorporated into the particle matrix because of the different drug binding sites present in the albumin molecule [154]. Nanoparticles made of albumin have specific advantages: they are biodegradable, easy to prepare and reproducible. Furthermore, albumin nanoparticles appear to be a suitable agent for gene therapy, because it might avoid undesired interactions with serum that are often encountered after intravenous injection of transfection complexes [155-156]

Albumin nanoparticles can be prepared by several techniques; desolvation, emulsification, thermal gelation and recently nano-spray drying, nab-technology and self-assembly techniques were also used. Due to the a range of drug binding sites present in the albumin molecule, one of the major advantages of albumin nanoparticles is their high binding capacity of various drugs. For the water soluble drugs; biodegradable polymers have low loading and encapsulation efficiency, albumin nanoparticles overcome this limitation. Water soluble drugs can be loaded to albumin nanoparticles either by incubation with the just-formed and hardened albumin nanoparticles or by incorporation of the drug into the solution of albumin prior to the formation and crosslinkage of the nanoparticles [157-158]. For water insoluble drugs, many researchers report the excellent incorporation of poorly soluble anticancer drugs into albumin nanoparticles by different techniques [159].Nab-technology [160-161] and self-assembly techniques were more prominent for encapsulating poorly soluble drugs.

AIM AND SCOPE

The main focus of this research work was on the preparation of a variety of nanostructured materials and gives their applications in various fields such as: as sensor, drug delivery vehicle and adsorbent.

A survey of literature reveals that semiconducting nanoparticles are capable, under certain conditions, of photoluminescence (PL). ZnS is a member of the important II-IV semiconductor family. ZnS nanoparticles have a wide band gap (3.6 eV) and photoluminescence in the ultraviolet (UV) range. These nanoparticles can be excited efficiently at any wavelength shorter than the emission peak yielding the same narrow and symmetric emission spectrum. They are very sensitive to surface interactions due to the unique discrete electronic state of each particle. The discovery of these luminescent nanoparticles has opened the door to a new exciting approach to fluorescent chemical sensing. By taking advantage of these properties of ZnS nanoparticles, a approach for iodide and menadione detection by PVP capped and calix[4]arene attached ZnS nanoparticles has been formulated.

Recent developments in nanotechnology have allowed new research approach in the field of drug delivery. Biodegradable polymers are able to provide superior drug delivery system for better management and treatment of diseases. These drug loaded polymeric nanocarriers have multiple advantages such as improved bioavailability and release profile of drug and reduces its toxicity by side specific targeting. The nano-scale structure of these carriers provides significant increases in surface area to volume ratio which results in notable behavior in in vitro and in vivo study as compared to the conventional formulation. Due to these benefits research work was undertaken for the development of nanostructured drug carriers such as nanocapsules, nanoemulsions and polymeric nanoparticles for some anticancer and antidiabetic drugs.

Considerable efforts have been made previously for the development of approaches for the synthesis of metal oxide and carbonate nanoparticles. Of these, nanocrystalline metal oxides and carbonate attract significant attention as effective adsorbent, sensor and antibacterial agent.

Among the several route to prepare metal oxide nanoparticles, the sol-gel technique is well known to provide pure and homogeneous particles. And hence in the present investigation, it was proposed to prepare magnesium oxide by simple and effective sol gel method and use as an antibacterial agent.

From an economic perspective, barium carbonate is one of the cheapest materials in nature. Barium carbonate has already been studied for heavy metal ions removal. The equilibrium adsorption of barium carbonate is of very short time, which makes it convenient in water treatment. Thus, other forms of barium carbonate should be considered, and we found that amorphous barium carbonate can be very efficient in water treatment with heavy metal ions. Water hardness and excess sulphate -related health hazards are a major environmental problem in many regions of the Gujarat and it is well known that barium carbonate has a good affinity to Mg, Ca and sulphate. Hence, it was proposed to prepare nanoform of barium carbonate to explore the possibility for water treatment.

Thus, in the present investigation it was proposed to prepare nanostructured materials based on metals, metal oxide, metal carbonate, metal sulphide and polymeric drug nanoparticles and apply the newly synthesized materials for sensing, for targeted drug delivery, for water treatment and finally for the evaluation of their biological activates.

Present investigation

In the present investigation the following work has been carried out:

Calixarene capped ZnS quantum dots as an optical nanoprobe for detection and determination of menadione.

A PVP assisted soft chemical synthesis method was used to prepare ZnS quantum dots. ZnSQDs were characterized by luminescence spectroscopy, ultraviolet-visible spectroscopy (UV-vis), FT-IR spectroscopy and transmission electron microscopy (TEM). The synthesized ZnSQDs were coated with p-sulfonatocalix[n]arene. The pSC[4]A-ZnSQDs assembly was found to be a highly sensitive sensor for menadione. After addition of menadione the fluorescence intensity of pSC[4]A-ZnSQDs was quenched. In the presence of other vitamins fluorescence of pSC[4]A-ZnSQDs remain unchanged, it reveals that this sensor is selective only for menadione. The quenching behaviour of menadione was investigated by the Stern– Volmer kinetic model.

Polyvinylpyrrolidone modified ZnS nanoparticles as a highly selective and sensitive fluorescence sensor for iodide (I-) in real samples.

A green and simple chemical synthesis of nano sized water soluble ZnS nanoparticles was accomplished by reacting anhydrous Zn-acetate, sodium sulphide and polyvinylpyrrolidone (PVP) at room temperature in aqueous solution. PVP modified ZnS nanoparticles were approximately 25 nm in diameter with strong and narrow photoluminescence properties with long term stability. This PVP capped ZnS nanoparticles were used as a fluorescent probe for detection of iodide ions. It has been observed that after addition of iodide solution the strong fluorescence of ZnS nanoparticles was almost quenched. Other anions showed little or no effect on the fluorescence of ZnS nanoparticles when tested individually or in mixture. In the presence of all other anions, iodide responded well and therefore PVP-capped ZnS nanoparticles used as a selective and sensitive sensor for iodide.

Microwave-assisted one-step rapid synthesis of glucose modified gold nanoparticles to improve drug delivery and enhanced potency of Pt-based anticancer drug for cancer treatment.

Glucose modified gold nanoparticles (DGNPs) were fabricated by one-step reduction of HAuCl4 by D-glucose under microwave irradiation. The morphology and size of the DGNPs was investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS).

Further, we developed the CPL-DGNPs conjugate and examined its cytotoxic effect and genotoxicity effect on ovarian cancer cell line by MTT and comet assay respectively. Spectroscopic examinations revealed that CPL can be directly bound onto DGNPs via the amine (-NH2) to form the CPL-DGNPs conjugate. The accumulation of CPL is faster and higher in ovarian cancer cell treated with CPL-DGNPs than that treated with equal dose of free CPL and CPL-GNPs. This can be attributed to the "concentrated effect" of CPL-DGNPs. The Comet assay confirmed that the CPL-DGNPs induced apoptosis rather than necrosis. The cellular uptake of CPL, CPL-GNPs and CPL-DGNPs were determined by HPLC for 15, 30 and 60 minutes.

Glucose coupled nanocarriers to enhance anticancer activity and targeted drug delivery

Glucose coupled nanocarrier was prepared by multiple emulsion-solvent evaporation technique using the biocompatible polymer PLGA and PVA as surfactant. The size and morphology of the nanocarrier was investigated by scanning electron microscope (SEM) and dynamic light scattering (DLS) studies. Drug was loaded into these nanocarriers and the interactions between the drug and the nanocarrier was evaluated by Fourier transform infrared spectroscopy (FT-IR), Proton nuclear magnetic resonance (1H NMR) spectroscopy and Differential scanning calorimetric (DSC). Cytotoxicity and genotoxicity studies on human leukaemia cell line were done by MTT and Comet assay respectively. The cellular uptake of Oxa, Oxa loaded dextrose coupled and uncoupled nanocarriers were determined for 15, 30 and 60 minutes.

Development and in vitro, in vivo evaluation of "Two-in-One" dual drug loaded polymeric nanoformulation for diabetes treatment.

Dual drug loaded nanoformulation (DDNF) was formulated by ionic geletion process of pioglitazone hcl dispersed chitosan and metformin hcl loaded eudragit nanoparticles. Here we used pioglitazone hcl(PIO) and metformin hcl (MET) as model anti-diabetic drugs. The size and morphology of the optimized DDNF was investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS) studies. Interaction between drugs and polymers were investigated by Fourier transform infrared spectroscopy (FT-IR) and Differential scanning calorimetric (DSC). In vitro drug release profile of both drugs was studied in biphasic medium. Drug release mechanism was also investigated by different kinetic models such as Higuchi and Korsmeyer. The in vivo study of these DDNF was examined on adult male wistar rats.

Synthesis and characterization of poly(lactic acid) - magnesium oxide nanocomposites and their synergistic effect on antibacterial activity and cytotoxicity

PLA-MgO nanocomposites were prepared in microwave by direct polycondensation of lactic acid with different loading ratio of magnesium oxide nanoparticles without using any catalyst. The structural properties, antiseptic and cytotoxic effects were investigated. The average molecular weight and thermal stability of nanocomposites are more than that of pure lactic acid. Fourier Transform Infrared Spectroscopy detected formation of hydrogen bonding between PLA chain and MgO nanoparticles. The particle morphology and size of MgO nanoparticles were studied by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) analysis. The antiseptic activities of nanocomposites were examined against gram-negative - Escherichia coli and S-Typhi and gram positive – Staphylococcus aureus and B subtilis bacterial strains by disc diffusion method. An in vitro cytotoxicity on human skin fibroblast cell line was measured by MTT assay. The aim of this study is to design hybrid nanocomposites, which imparts a new model to fight against bacteria.

Synthesis of PVP- stabilized amorphous barium carbonate nanoparticles for removal of sulphate and hardness from mine and industrial waste water.

Nanoparticles of BaCO3 were synthesized by the PVP-assisted soft chemical method. The nanoparticles were characterized by FT-IR, XRD, DSC, DTA, SEM and DLS analysis. The ability of the BaCO3 Nps for removal of sulphate and hardness from aqueous solution has been investigated. Removal of sulphate and hardness were investigated by ion chromatography. Effect of various parameters viz. contact time, pH effect (pH 2–10), dose of nanoparticles (0.01–0.1 g/100 ml), initial sulphate / calcium and magnesium concentration (0.01–10 mg L-1) and competitive ions has been investigated to determine to sulphate and hardness removal capacity of BaCO3 nanoparticles. A precipitation transformation mechanism is proposed to play a key role in such water treatment.