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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 3  |  Page : 479-486

Application of nanotechnology in cancers prevention, early detection and treatment


1 Department of Emergency Medicine, Wayne State University, USA
2 Department of Oncology, Apollo Hospital, Ahmedabad, India
3 Department of Medical Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication14-Oct-2014

Correspondence Address:
Shraddha P Patel
Department of Emergency Medicine, Wayne State University
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.138196

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 > Abstract 

Use of nanotechnology in medical science is a rapidly developing area. New opportunities of diagnosis, imaging and therapy have developed due to recent rapid advancement by nanotechnology. The most common areas to be affected are diagnostic, imaging and targeted drug delivery in gastroenterology, oncology, cardiovascular medicine, obstetrics and gynecology. Mass screening with inexpensive imaging might be possible in the near future with the help of nanotechnology. This review paper provides an overview of causes of cancer and the application of nanotechnology in cancer prevention, detection and treatment.

Keywords: Diagnosis, imaging, nanoparticles, nanotechnology, targeted delivery


How to cite this article:
Patel SP, Patel PB, Parekh BB. Application of nanotechnology in cancers prevention, early detection and treatment. J Can Res Ther 2014;10:479-86

How to cite this URL:
Patel SP, Patel PB, Parekh BB. Application of nanotechnology in cancers prevention, early detection and treatment. J Can Res Ther [serial online] 2014 [cited 2019 Oct 13];10:479-86. Available from: http://www.cancerjournal.net/text.asp?2014/10/3/479/138196


 > Introduction Top


Cancer is a genetic disease. [1] In normal condition, cell division is controlled by the apoptosis complex. [2] The apoptosis complex is activated by tumor suppressor protein P 53 and the tumor necrosis factor. When both mechanisms malfunction, cells undergo uncontrolled cell division and grow to malignant tumor. [3] Capillaries grow abnormally within the tumor. The malignant tumor obtain nutrients from the surrounding healthy tissue. [4] When the tumor is enlarged, some tumor cells enter the blood stream and eventually invade other parts of the body and form other tumors. This phenomenon is known as metastasis and is a fatal condition. [5]

Nanotechnology is an upcoming technology that may change current cancer diagnosis and treatment methods. [6] Nanotechnology covers a broad range of topics; therefore, it is called a multidisciplinary field, which includes biology, physics, chemistry and engineering. [7] The main idea in nanotechnology is fabrication and control of material at the nanoscale. Nanotechnology has provided a way for rearranging and restructuring matter on an atomic scale and hence that we can understand the root of any problem. [8],[9] Nanoparticles are microscopic particles with size in nanometers (1-100 nm). [6] For example liposomes, dendrimers, quantum dots, gold (Au) containing nanoparticles (raman probes), super paramagnetic iron oxide (SPIO) nanoparticles, silver (Ag) oxide nanoparticles, nanosphere [Figure 1], carbon nanotube [Figure 2] and halloysite [Figure 3]. The use of these nano-sized systems in biomedical application is nanobiotechnology. The use of nanobiotechnology in detection, diagnosis and treatment of cancer is cancer nanotechnology or nanooncology. [6],[10]
Figure 1: Nanosphere

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Figure 2: Carbon Nanotube

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Figure 4: Nanopatterns produced by photolithography

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Nanoparticles can be classified depending on the major building material present. [11],[12] Depending on the building material, nanoparticles are of two types, organic and inorganic nanoparticles. [6] Liposomes, dendrimers and carbon nanoparticles are good examples of organic nanoparticles. [12] Quantum dots, gold (Au) containing nanoparticles (raman probes), SPIO nanoparticles, silver (Ag) oxide nanoparticles are examples of inorganic nanoparticles. [12],[13]

Nanovectors and defined surface patterning are two major subfield of nanotechnology. Nanovectors are very important for the administration of targeted therapeutic and imaging agents. [7],[14] Liposomes are a good example of nanovectors. [15] Nanoscale resolution is possible with electron beam lithography, ion beam lithography, layer-by-layer (LbL) assembly etc. [16] Nanocantilevers and nanowires are good examples of multiplexing nanotechnology. [17]

Due to the unique properties of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins all are used as building blocks for bottom up nanofabrication. [18],[19] The mortor pRNA of bacteriophage phi29 forms dimers, trimers and hexamers. This phi29 pRNA can be altered to form a distinct shape and structure, which can be used as RNA array. [20] Many nanovectors are being studied. By properly combining them with appropriate therapeutics and targeting moieties, it might be possible to develop personalized therapeutic drugs. However, the field of nanotechnology is quite young and we are still trying to understand its potential.


 > Benefits of nanoparticles Top


Partial size and surface characteristics can be changed according to need. Therapeutic efficacy can be increased and side-effects of drugs can be reduced by using nanoparticles, which control sustained release of a drug. [6],[11] With the help of matrix selection, we can control the release and partial degradation of nanoparticulate systems. Targeting legends can be attached to the surface of nanoparticles so that we can do site specific targeting. [21],[22] Many different routes can be used for inserting nanoparticles in the body. [11] Multifunctional nanoparticles can be used for both therapeutic and/or imaging. [7]


 > Characteristics of nanoparticles Top


Drugs are absorbed after the formation of nanoparticles. Ideally, the drug loading capacity of nanoparticles should be high. [11] Release of a drug is dependent on its diffusion, the degradation of the matrix, solubility, adsorption, combination immunogenicity, hydrophobicity, hydrophilicity, zeta potential and the surface property of nanoparticles. [11],[23] Targeting ability, in vivo distribution and toxicity of nanoparticles are determined by their size and size distribution. Nanoparticles have higher intracellular uptake and the ability to cross the blood-brain barrier. [11],[23] Nanoparticles have the ability to release drugs faster because of the larger surface area. [11]


 > Materials and methods for manufacturing nanoparticles Top


According to literature, different bottom-up and top-down methods are used for preparation of different nanoparticles. [24] The top-down method starts with a bulk material, which is then broken into smaller pieces using mechanical, chemical or other forms of energy. The bottom-up method is the opposite approach to the top-down method. The bottom-up method involves synthesizing the material from atomic or molecular level via chemical reactions, allowing the precursor particles to grow in size. [25],[26] Photolithography, electron beam lithography, ion beam lithography, atom lasers, systematic evolution of ligands by exponential enrichment (SELEX), co-precipitation and LbL assembly are a few selected examples for methods of preparing different nanoparticles. [11],[23],[24] Different methods are used depending on the required size of nanoparticles, surface characteristics, biocompatibility, biodegradability, properties of the drug and its release profile and antigenicity. [11] Protein, polysaccharides and synthetic polymers can be used for preparation of nanoparticles.

Lithography

Lithography is a method of printing on the surface. Nanolithography refers to writing, printing or etching at the microscopic level where dimension of characters are in the order of nanometres. There are different types of lithography, for example, photolithography, electron beam lithography and ion beam lithography and atom lasers.

Photolithography

Photolithography is used for the fabrication of micro and nano-size patterns. In this method, light is used for transferring patterns to the substrate, for example, nanopores, hydrophobic chemical surface and biological moieties patterns [Figure 4]. [7]
Figure 5: Electron beam lithography

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Electron beam lithography

Electron beam lithography is one of the best established methods of writing on at nanoscale surface. It uses a beam of electrons for writing on the surface [Figure 5]. This method works best for creating a one-off (single) nanostructure, but it is not appropriate for mass production. [27]
Figure 6: Atom laser

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Ion beam lithography

In ion beam lithography, a beam of ions is used instead of the beam of electrons for writing. These ions are charged; they can interact physically and chemically with the exposed material and can also settle on it. This method can be used for the bottom-up fabrication method. [28]

Atom lasers

Atom lasers are a beam of coherent atoms [Figure 6]. This allow the building up of layers of different materials at nanoscale. [29]
Figure 7: Nanowiers

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Co-precipitation

Iron-oxide particles have ferromagnetic properties, which are unique and can be used for many different bio-applications. The most common method for the fabrication of ferrimagnetic iron oxide nanoparticles is by the co-precipitation of ferrous and ferric ions in the solution. Yu and Hariani used very similar methods to fabricate nanoparticles. [30],[31] They used mix powder of iron (II) chloride and irons (III) chloride and then dissolved in an acidic solution. Afterwards, this solution was added to another basic solution for the precipitation of nanoparticles. Shi Yu created a ferrous and ferric ion solution by dissolving 3.25 g FeCl 3 and 2 g FeCl 2 .4H 2 O powder in the solution of 50 ml of DI water and 10 ml of 1 M HCl. This solution was then added drop-wise to 100 ml of 1 M NaOH. This reaction was carried out in an inert atmosphere. High purity argon was purged though the reactor. The reaction mixture was stirred for an additional 30 min; and then the solution was centrifuged at 5000 rpm. The decantation process was used to remove a supernatant solution from the precipitate. Once lees were collected, they were washed with the DI water. Then they were used for the further experimentation or analysis. X-ray diffraction was used to find the atomic structure of crystals. In addition, scanning electron microscopy and transmission electron microscopy were used to find the morphology of the nanoparticles. Using these methods, Yu and Hariani were able to achieve mean size of 8 nm of iron-oxide nanoparticles. [30],[31]

SELEX technique

Normally, RNA contains different single stranded loops for inter and/or intra molecular interactions. [32],[33] These loops can be used for mounting different nanoparticles. [34],[35] Self-assembly of nanoparticles can be done in two different ways, through template and non-template assembly. [20],[36] Template assembly is based on interactions of RNA molecules under the influence of the specific external force, external sequence, transcription, hybridization or annealing. Non-template assembly includes chemical conjugation, loop-loop interaction of RNA, ligation and covalent linkage. [20] The SELEX technique can be used for detection of distinctive RNA/DNA molecules from the huge population of the DNA/RNA library. [20]

LbL assembly

The LbL assembly technique is a bottom-up nanofabrication technique. It is used for the fabrication of multilayer thin films. In this method, different materials can also be incorporated within the different layers, for example, biomolecules and nanoparticles. [37],[38] These thin films are formed by deposition of alternating layers of oppositely charged materials (negatively and positively charged polyions). Between every step, a washing step is performed. There are many different ways to create LbL dip coating, spray coating and spin coating. [39] The characterization of LbL film is performed by quartz crystal microbalance (QCM). [38]


 > Uses of nanoparticles Top


Nanoparticles can be used for imaging, diagnostics and drug delivery [Table 1].
Table 1: Early detection, imaging, diagnosis and drug delivery with and without use of nanotechnology

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Biosensors and diagnostics

Biosensors can be used in vivo and in vitro diagnostics. Examples of biosensors are nanowires [Figure 7], nanocantilevers [Figure 8] and quantum dots [Figure 9]. These biosensor can be used for measuring pH and for detecting chemical and biological species. [40] The nanocantilevers monitor multiple serum protein markers and can also be used for measuring the content of specific DNA. [7] With the help of fluorescent nanocrystals (quantum dots) linked with antibodies or DNA probes, we can detect the specific protein or DNA targets. [12],[40],[41] Real time monitoring of the release of the protein or antibody can be done by in vivo nanosensors. In the future, it may be used with signaling and therapeutic delivery devises. [40],[41]
Figure 8: Nanocantilevers

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Figure 9: Quantum dot

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Figure 10: Multifunctional nanoparticle

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Drug delivery and therapeutics

The present drug delivery system has many problems; a toxicity to non-targeted tissues, difficulty in maintaining the drug level and metabolism problem. Other problems are drug solubility and cell permeability. [11],[40] All these problems can be solved with the nanotechnology based delivery system. Targeting, diagnostics and therapeutics can be done simultaneously by use of multifunctional nanoparticles [Figure 10] and [Figure 11]. [7],[11],[12],[40],[42] Bioavailability can be improved by encapsulated or eroded self-assembled structures, for example, polymeric nanoparticles. [11],[40],[43] These will help in controlling the initial dose and also widen the therapeutic window and hence that effectiveness could be improved. Neoplastic cells and protein expression can be used as target tissue in viral infection and mediator of inflammation. The trigger release of drugs depend on the internal or external signals, such as pH, near infrared, ultrasound and radio frequency. [44]
Figure 3: Halloysites[67]

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Figure 11: Targeted drug delivery

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Injectable nanovectors are important for cancer treatment, as they can be injected intravascularly. [7] They can be used for the non-invasive, in vivo visualization of the molecular marker of diseases and targeted drug delivery with reduced side effects. A liposome is an example of the simplest form of the nanovector. [45] Doxorubicin encapsulated in liposome was approved for Kaposi's sarcoma. Now this drug is used for breast and ovarian cancer. [7],[46]

Small interfering RNA (siRNA) is 20-25 nucleotide molecules of RNA. It is produced when large pieces of RNA are cleaved. [20],[47] Its role is to obstruct gene expression through cleavage of messenger RNA by a protein/RNA complex know as RNA induced silencing complex. [48] Antisense RNA is transcribed in a direction opposite of the target RNA from the same DNA transcript. Antisense RNA technology provides ways by which RNA/RNA interactions can be unfailingly probed. [20],[49] They have many applications in nanotherapeutics. RNA or DNA based oligonucleotides are known as aptamers. Aptamers can detect many different kinds of molecules, such as nucleotides, proteins, peptides, organic compounds and receptors. [50] Some cancer cells over-express folate receptors, which are absent in normal cells. The folate molecules bind to folate receptors with great affinity. [51] Thus, with the help of in vitro transcription, a folate molecule is integrated at the 5΄ end of RNA, using folate- AMP(Adenosine monophosphate). The experiment was performed on mice. The group of mice, which received only cancer cells developed tumors within 3 weeks. Another group of mice that received cancer cells treated with the pRNA complex (folate-pRNA and pRNA/siRNA) did not develop tumors. [20]

Imaging

The anatomy and physiology of disease can be studied with current imaging techniques, but pathways involved in disease processes cannot be studied. To study detailed pathways non-invasively in vivo, quantum dots, self-assembling nanoparticles, targeted probes and target multivalent dendrimers are used. Although, ultra-sonography is standard in medical practice with the help of micro bubbles and nanomolecular agents, its use can be improved. It is the hottest field in molecular imaging. [42] It works on the principle of contrast enhancement of organs, that they are usually emulsions of perfluorocarbon encapsulated in lipid sphere. Ultra-sonography is useful in diseases in which blood vessels are involved, for example fibrin thrombin, atherosclerotic plaques, mayocarditis, transplant rejection etc. [40],[52] However out of all the fields, physiopathology is the most promising field. It can identify small vessels and neovascularization, which is common in all cancers. These vessels are irregular, abnormal and cannot be detected by ultrasonography alone, but with the use of ultrasonography contrast media (UCM), we can identify a cancer in early stages. This will change the prognosis. Ultrasonography is mainly used in obstetrics and gynecology. For example, an endometrial cavity cannot be studied by ultrasonography alone, but with the help of UCM, it is possible. [40],[42],[52]

Several different types of nanoparticles have been used clinically and in research protocols, such as gadolinium and iron oxide based nanoparticles. [53],[54] Multifunctional nanoparticles are also very important, as they can perform multiple tasks, for example, targeting biological moieties, acting as a contrast agent and are also in detection. [6],[55] Immunotargetted drugs usually deliver a large amount of therapeutic or imaging agents. [56] According to the size and the property of nanovectors, a covalently linked antibody is used. [57] Nanoparticles are prepared to reduce degradation of active agents from environmental and/or enzymatic degradation. [58] For example, iron-oxide [Figure 12] can be used for magnetic resonance imaging (MRI) and/or semiconduction. [59] Another example is the quantum dot, which can be used for optical imaging. [60] Dendrimers are a self-assembling polymer, which creates nanovectors. [61] These nanovectors are recently used in the MRI of the lymphatic system in the mouse model with breast cancer. [62] This indicates that there is a very good chance that non-invasive detection of cancer cells in the lymph node of patients could be possible in the near future. Therefore, this means that we can detect an early disease and pattern of metastatic spread.
Figure 12: Super paramagnetic iron oxide

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Porosified silicon is biodegradable. [63] It has more kinetics (minutes to hours) than biodegradable polymers (weeks to months). Metal-based nanoshells contain a gold layer over the silica core. The thickness of the gold layer can be decided according to the need. This can be selectively activated through tissue irradiation. [8]

Real-time vital optical imaging

Early diagnosis is the single most important challenge in oncology. The majority of cancers are epithelial in origin. A mass screening of the asymptomatic population is very expensive and impractical. With the help of vital microscopy, we can study a three-dimensional picture of the tissue microanatomy. These diagnostic systems are inexpensive and easily portable, so they can be used in early diagnosis of superficial lesions. [10]


 > Conclusion Top


Nanotechnology is a new and expanding technology; its main applications are cancer diagnostics, targeted delivery and imaging. Preliminary results in cancer research shows that the use of nanotechnology in clinical practice is going to change current cancer detection and treatment methods. Different authors have described its clinical value in many other areas of human diseases. After studying in great detail, The National Cancer Institute has regarded this as an area of major importance and has awarded excellent grants to many centers. Poorly soluble and labile drugs can now be delivered to the targeted sites with the minimum dosage and the minimum toxicity. The limitation of current passive methods will be overcome in the future by highly-motile, small nanoparticles. [64] Nanoscopy will resolve morphological and physical properties of neuronal-iron channels. [65] In the future, nano vectors will selectively bind to neo-visualization and will act as a very early diagnostic agent and will trite it at a very early stage. [7] Individualizing therapeutics will be possible.[67]

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 11], [Figure 12]
 
 
    Tables

  [Table 1], [Figure 10]



 

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