The fascinating aspect of these materials stems from the fact that when certain particles or devices are manufactured on the nanometer size region by means of special chemical and physical methods, they start showing distinct properties dependent on size, shape, and elemental compositions (such as huge amount of light absorption/emission, plasmonic resonance, high surface area, ability to convert light into heat, desirable magnetic properties, etc). Each of these features have found many applications in technology and they provide superior properties when compared to conventional materials. This article will not cover each technology based on nanomaterials but rather focus on the medical aspects and applications of nanotechnology and the direction it is heading.

Nano-medicine is a novel branch of nanotechnology seeking to deliver medically relevant drugs and imaging agents to the desired sites of the body. Biomedical imaging and drug delivery fields are benefitting from nanotechnology to a greater extent because not only do nanomaterials provide unprecedented results in diagnosis and therapies, considerable amounts of incentives in the form of governmental and private funding also drive topnotch institutions and scientists to study these materials around globe. For instance, iron oxide—when designed and manufactured on the nanometer order—can compete with, if not replace, most of the commercial magnetic resonance imaging (MRI) contrast agents due to some of its attributes, (i.e., being much more sensitive) requiring a less amount compared to other contrast agents, non-toxic to humans, and easy to manipulate in terms of its chemistry (1). Nanometer-sized spherical and rod-shaped Cadmium/Tellerium/Lead sulfides and selenides, also known as “Quantum Dots,” can absorb and emit light from ultra-violet (UV) to infrared region (IR) and this phenomenon could be utilized to construct biomedical sensors capable of detecting biologically relevant species (such as blood glucose, tumor markers, hormones, and etc.) with great accuracy and speed (2). Even by using multiple colors emitting “Quantum Dots,” one can, in principle, detect more than one biological entity simultaneously. Furthermore, their superior emissive properties could be harnessed to develop sensitive and selective fluorescence imaging techniques and assays which can lead to simple and early diagnosis of diseases. Gold nanorods, if irradiated with IR lasers, can generate extreme local temperatures in the surrounding medium owing to “plasmonic resonance of surface electrons,” and this feature could be directed to killing of localized tumor tissues known as “Photothermal Theraphy” (3).

Another class of nanomaterial called liposomes (4) can actually mimic lipid bilayer of the cell membrane which gives rise to a protective layer around organelles and nucleus, and maintains the transport of ions and molecules in and out of the cell. Synthetic liposomes, strikingly, can accommodate various cargoes extending from drugs to imaging agents in their inner cavity and render controlled release of its cargo as it circulates in the body, thereby providing longer bio-availability.

One of the most alluring uses of nanoparticle formulations in cancer therapy is their dimension. Certain sizes of nanoparticles can permeate into tumoral sites and be retained in that region longer than small particles or molecules. This extraordinary feature of nanoparticles, called “enhanced permeability and retention effect” (5), was utilized with liposomes to deliver chemotherapeutics to cancerous tissues effectively in a slow and controlled manner. In addition, chemical malleability of nanoparticles give rise to smart formulations which could respond to external stimuli in drug delivery applications. For example, the fact that cancer cells have lower pH values as compared to normal cells has been used to trigger release and delivery of drugs on site (6).

An alternative approach to conventional treatments is gene therapy in which the malfunctioning or mutant gene has been reintroduced into cells with a properly functioning one in order to restore the malady (7). Nanoparticles, especially polymeric counterparts, have shown promising results in encapsulating, carrying and delivering the gene of interest into desired cells.

Apart from synthetic nanoparticles, naturally occurring nanoparticles, have lately received great attention due to their unique structures and properties such as biocompatibility, uniform size, as well as suitability to chemical and genetic engineering. Plant and bacterial viruses, known as viral nanoparticles (8), have been tested for imaging and drug delivery applications, and because they infect only plants and bacteria, they are considered to be benign towards mammalians. Their inner and outer amino acids could be chemically modified with drugs and imaging modalities and cleverly engineered drug release mechanism could be invoked to operate upon external or internal stimulus.

Nanomaterials are, furthermore, suitable candidates for vaccine development. The immune system normally recognizes certain chemical groups on the surface of antigens (pathogens) and develops its defense mechanism based on this recognition. Multiple copies of these chemical groups could be chemically tailored around the surface of nanomaterial, and thereby could trigger the same immune response more efficiently (9).

The future of medicine will be shaped and enhanced through a targeted delivery of drugs and imaging contrasts into desired sites. Promisingly, nanoparticles will be able to assist in this regard to a considerable extent. Today’s cancer chemotherapy rely mostly on administering a variety of cancer drugs via intravenous (injecting through the vein) or oral means which delivers drugs to cancer cells as well as a considerable amount to healthy tissues which causes major side effects. In order to accumulate higher doses of drugs in tumor cells selectively and minimize nonspecific delivery, nanoparticles loaded with drugs and chemically decorated with “smart molecules” which have the ability to recognize cancer cells and specifically bind to them have been designed and tested successfully (10). These smart groups (organic molecules, antibodies, peptides and small molecules), surprisingly, have higher binding affinities toward some receptors over-expressed in cancer cells. Furthermore, encapsulation of drugs by nanomaterials provides a protective shell which prevents leakage of drugs to other sites.

An important drawback of cancer therapy is drug resistance in which cancer cells develop mechanisms to pump chemotherapeutics out of cells and decreases the efficacy of drugs. Nanoparticles, however, invalidate these resistance mechanisms by encapsulating drugs and should therefore not be exposed directly to surrounding cell environment. When nanoparticles reach the desired destination in the cell, an engineered mechanism or stimulus augment the release and drugs are expected to show their activity without any compromise (11).

It is fascinating to see how these small nanoparticles behave cleverly and orderly even though they look like inanimate and unconscious clusters of atoms. The extraordinary art, design and engineering witnessed in macro dimensions can also be seen in nano dimensions which means that a conscious and purposeful Hand of Power is present and visible in this nanoworld.

To sum up, nanomaterials could be ideal platforms for drug delivery and imaging applications and could complement the deficiencies in conventional therapies. Loading multiple copies of these entities into nanoparticles and devising clever mechanisms to target and deliver them into desired sites would be key elements in the nanomedicine of the future. We are living in a world where each of us has someone in our families or among our friends who are going through painful cancer treatments, which is a heart-rending and traumatic experience. Hopefully, nanomaterial-based therapies would give rise to solutions and success in battling against cancer. For in one prophetic tradition the Prophet Muhammad, peace be upon him, says: “O servants of God! Search for ways for treatment of illnesses. If God gives you ailments, for sure He bestows upon you cures for those.”

And why can’t this bestowal be in the nano form?

References

• Qiao RR, Yang CH, Gao MY. “Superparamagnetic iron oxide nanoparticles: from preparations to in vivo MRI applications” (vol 19, pg 6274, 2009). J Mater Chem 2009;19:9286-9286.
• Raymo FM, Yildiz I. “Luminescent chemosensors based on semiconductor quantum dots.” Phys Chem Chem Phys 2007;9:2036-2043.
• Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA. “Gold Nanoparticles for Biology and Medicine.” Angew Chem Int Edit 2010;49:3280-3294.
• Jesorka A, Orwar O. “Liposomes: Technologies and Analytical Applications.” Annu Rev Anal Chem 2008;1:801-832.
• Sancey L, Barbier E, Hirsjarvi S et al. “Enhanced Permeability and Retention (EPR) effect in tumors: characterization by MRI and fluorescence imaging.” B Cancer 2011;98:S67-S67.
• Hruby M, Konak C, Ulbrich K. “Polymeric micellar pH-sensitive drug delivery system for doxorubicin.” J Control Release 2005;103:137-148.
• Waehler R, Russell SJ, Curiel DT. “Engineering targeted viral vectors for gene therapy.” Nat Rev Genet 2007;8:573-587.
• Yildiz I, Shukla S, Steinmetz NF. “Applications of viral nanoparticles in medicine.” Curr Opin Biotech 2011;22:901-908.
• Peek LJ, Middaugh CR, Berkland C. “Nanotechnology in vaccine delivery.” Adv Drug Deliver Rev 2008;60:915-928.
• Ruoslahti E, Bhatia SN, Sailor MJ. “Targeting of drugs and nanoparticles to tumors.” J Cell Biol 2010;188:759-768.
• Liang XJ, Chen C, Zhao Y, Wang PC. “Circumventing tumor resistance to chemotherapy by nanotechnology.” Methods Mol Biol 2010;596:467-88.

Nanoscience and nanotechnology started off in the early 1980s when scientists were able to detect materials on the nano-level through microscopic systems. This development enabled the synthesis of nano-level materials such as carbon nanotubes, nano crystals, and metal oxide nanoparticles. Nanotechnology is a type of technology, resulting from the research conducted on the atomic, molecular and macromolecular levels. A nanometer is one-billionth of a meter. Nano-level studies are conducted with materials whose sizes range between one to a hundred nanometers. Studies on the nano-level are conducted in the contemporary science fields such as chemistry, materials science, physics, biology, etc. One of the most compelling reasons that renders the research with nano-level materials so significant is that nanoparticles reflect a lot more different characteristics than when they do at the macro-level. Due to their small sizes, nanoparticles, especially those under 20 nm, have magnificent optical, magnetic, and chemical properties.[1] Nanoparticles include much more energy than the macro-level materials; this is because the ratio of the surface area of nanoparticles to their volume is much more bigger than the ratio in macro-level materials. A significant amount of energy is stored in nanoparticles as free surface energy. This energy revealed on the nano-level not only increases the reactivity of iron nanoparticles (the propensity to chemical reactivity), but also renders the magnetic qualities of materials quite differently than they would be at the macro-level.

Many types of nanoparticles are widely used in our daily lives. Iron, gold, silver and cadmium sulphide nanoparticles are some of the most commonly investigated nanoparticles. Yet iron nanoparticles receive special attention from scientists essentially in the field of biotechnology. Iron nanoparticles demonstrating different magnetic features have a wide range of use in fields, including but not limited to health care and electric/electronic industry. Owing to its magnetic feature, iron is also used in magnetic recording. The production of needle-shaped iron nanoparticles with high magnetic features has facilitated the manufacturing of mobile electronic devices with a high recording capacity. In this paper, we will focus on the use of iron nanoparticles’ contribution to the advances in the field of biotechnology, among numerous other contributions of iron nanoparticles in other fields.

Nanobiotechnology

Nanobiotechnology, among other fields of nanotechnology, is the field that focuses on biological systems. Nano-level devices designed to work with biosystems, nano-level cell biology, cell and nanoparticle interactions are some of the applications used in nanobiotechnology. Through those applications, biochemical processes and reactions in living beings can be scrutinized in great detail, which, in turn, enables scholars to come up with innovations in both diagnosis and treatment of various illnesses.

The following are the primary application areas of magnetic nanoparticles in the field of bionanotechnology: development of magnetic resonance imaging systems, and cancer research. Especially, iron oxides (magnetite, Fe3O4, maghemite, Fe2O3), owing to their cohesion with the chemical structure of biological systems, are prevalently used in biotechnology.

Magnetic Resonance Imaging (MRI)

MRI, mostly used in the medical field, is the method to monitor the internal structure of living mechanisms. Through the magnetic area and radio frequency waves, the image of a living tissue is formed. MRI is a complex system that produces images based on the intensity and movements of hydrogen atoms in the tissue. The MRI technique is used to diagnose almost all sorts of illnesses today. Yet it is most frequently used with illnesses pertaining to the central nervous system, brain and spinal cord. It has also been used to diagnose muscle-related and skeleton-related medical conditions, such as meniscus and herniated disc symptoms, as well as all types of neurological illnesses. MRI has not been found detrimental to any living organism thus far.

It is the paramagnetic ions such as gadolinium that are most frequently used as contrast enhancement agents in MRI applications. Although gadolinium has a high moment, this moment is too low compared to superparamagnetic materials. For this reason, superparamagnetic iron oxide nanoparticles are known to be more efficient MRI contrast enhancement agents. Known as such, those iron oxide nanoparticles are quite advantageous over gadolinium. Those nanoparticles can easily be functionalized to interact with biological samples. For example, superparamagnetic nanoparticles, which are not normally taken up by cells efficiently, can do so after being covered with another material (e.g. Dextran) that can ordinarily go into a cell. Thus, MR images of particular tissues could be obtained clearly, which enables us to make more accurate diagnoses and treatments.

Iron oxide nanoparticles are also deemed to be an efficient potential future method in cancer treatment. The results of several studies conducted to fulfill this goal are encouraging.

Iron oxide superparamagnetic nanoparticles are being tested as a method in hyperthermia treatment. Hyperthermia is defined as an abnormally high body temperature, and its treatment is carried out through the removal of certain tissues by increasing its temperature up to (42–46) 0C for 30 minutes. For instance, cancer infected liver tissues are exterminated through the hyperthermia method, which sends biologically activated iron oxide nanoparticles to those infected tissues. Moreover, none of the healthy tissues are damaged during this process. You may find more detailed information in references [1, 2, 4, 6] on how nanoparticles are aptly sent to the cancer infected tissues only while the surrounding healthy tissues remain unaffected by them. Hundreds of researchers carry out experiments and publish their findings on this topic everyday. Yet, further research needs to be done in order to reach solid conclusions.

Iron, which seems to carry greater potential significance than we previously thought, should receive much attention from scholars due to the fact that a chapter (surah) in the Holy Qur’an is entitled “Iron” (Hadeed). The question is, why was a 29-line chapter in the Qur’an is called (Iron) when the word “iron” was only mentioned once throughout the entire chapter.

The chapter “Iron” first begins by drawing the reader’s attention to the attributes and praised names of God. It invites people to believe in God and his messenger Muhammad (peace be upon him) by exalting God as the Almighty, Sovereign, Ruler, One whose existence is without a beginning and an end, Manifest and Hidden. Then, the chapter goes on to encourage believers to donate their wealth for the sake of God, for those who follow the word of God are rewarded with a place in Heaven. It also advises believers never to lose their ardor, while reminding them that even the earth will be resurrected after all has perished. And the wisdom behind the creation of iron is explained as such:

Assuredly We have sent Our Messengers with manifest truths (and clear proofs of their being Messengers), and We have sent down with them the Book and the Balance so that (relations among) humankind may live by equity. And We have sent down iron in [the essence] which is stern might and benefits for humankind, so that God may mark out those who help (the cause of) God and His Messengers, though they do not see Him. Surely God is All-Strong, All-Glorious with irresistible might. (57:25)

This particular verse includes several remarkable points. First, the very use of the phrase “sending down” for iron is so striking that it was also mentioned in [3, 5]. Another perplexing statement is, We sent down iron in [the essence] which is stern might and benefits for humankind, which might pave the way for thought-provoking venues regarding nanotechnology. The verse also indicates that which makes iron so special, its indiscernible or hidden qualities, rather than the outer surface of it. The specific reference to the “essence” of iron hints at this point. If the message of the verse had been related to the external qualities of iron, then the choice of the words would differ accordingly. Since the Qur’an is the word of God, there is wisdom behind the selection and sequencing of each word and letter. From this point of view, we can interpret that this verse informs us about the significance of the essence of iron on the nano level.

The significance of iron as stated in a single verse of the Qur’an has been briefly discussed. Numerous studies on the use of iron in nanotechnology seem to be on the horizon, which will only contribute to our admiration for the miracle of the Qur’an.

Kamil Ezgin is pursuing a PhD degree in chemistry in USA. For correspondence with the author kamilezgin@gmail.com.

References

1. Dale L. Huber. Synthesis, Properties, and Applications of Iron Nanoparticles, small, 2005, 1, No. 5, 482-501.
2. An-Hui Lu, E.L. Salabas, and Ferdi Schuth, Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application, Angew. Chem. Int. Ed. 2007, 46, 1222-1244.
3. Edib Masûkî. “Enteresan Bir Tespit: Demirin Sakladiði Sir,” Sizinti, 1985, No. 73.
4. Peter Majewski and Benjamin Thierry. “Functionalized Magnetic Nanoparticles- Synthesis, Properties, and Bio-Applications,” Critical Reviews in Solid State and Materials Sciences, 2007, 32, 203-215.
5. http://www.mergeous.com/bullet.asp?tag=72
6. Volker Mailander and Katharina Landfester, “Interaction of Nanoparticles with Cells,” Biomacromolecules 2009, 10, 2379–2400.