Health & Medicine

  • Issue 93 / May - June 2013



    Nanomedicine : A Novel Paradigm to Medicine

    Ibrahim Yildiz

    Nowadays, we have been accustomed to hear “nano-something,” and we hardly pay any attention to what this really means to us in our daily life. From the perspective of material science, nanoscience or nanotechnology deals with innovations and productions of materials on a nanometer scale (10-9 m) which exhibit unique properties with respect to their sizes and compositions. In general, such technologies could find applications in a variety of fields such as medicine, electronics, material sciences, etc.
    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
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    2. Raymo FM, Yildiz I. "Luminescent chemosensors based on semiconductor quantum dots." Phys Chem Chem Phys 2007;9:2036-2043.
    3. 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.
    4. Jesorka A, Orwar O. "Liposomes: Technologies and Analytical Applications." Annu Rev Anal Chem 2008;1:801-832.
    5. 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.
    6. Hruby M, Konak C, Ulbrich K. "Polymeric micellar pH-sensitive drug delivery system for doxorubicin." J Control Release 2005;103:137-148.
    7. Waehler R, Russell SJ, Curiel DT. "Engineering targeted viral vectors for gene therapy." Nat Rev Genet 2007;8:573-587.
    8. Yildiz I, Shukla S, Steinmetz NF. "Applications of viral nanoparticles in medicine." Curr Opin Biotech 2011;22:901-908.
    9. Peek LJ, Middaugh CR, Berkland C. "Nanotechnology in vaccine delivery." Adv Drug Deliver Rev 2008;60:915-928.
    10. Ruoslahti E, Bhatia SN, Sailor MJ. "Targeting of drugs and nanoparticles to tumors." J Cell Biol 2010;188:759-768.
    11. Liang XJ, Chen C, Zhao Y, Wang PC. "Circumventing tumor resistance to chemotherapy by nanotechnology." Methods Mol Biol 2010;596:467-88.


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