Nanomedical Devices: An overview

Geeta M Patel

A new era on medicine are expected to happen in the coming years.

Due to the advances in the field of nanotechnology, nanodevice manufacturing has been growing gradually. Some medical nanodevices may have mobility - the ability to swim through the blood, or crawl through body tissue or along the walls of arteries. Others could have different shapes, colors, and surface textures, depending on the functions they would be intended to perform. They would have different types of robotic manipulators, different sensor arrays. Each medical nanodevice could be designed to do a particular job extremely well, and would have a unique shape and behavior. The most elementary nanomedical devices are used to diagnose illness and to repair damages and infections.

Introduction:

Nanomedicine is the comprehensive monitoring, control, construction, repair, defense, and improvement of all human biological systems, working from the molecular level, using engineered nanodevices and nanostructures. The prefix “nano-“comes from the Greek root nanos, or dwarf and means one-billionth 10^-9of something ¹. Though this discipline is in its infancy it will has the potential to change medical science in the future.

Nanomedicine includes three progressively more powerful molecular technologies (Table-1). The first one compasses nanoscale-structured materials and devices.The second is the raw material and the third includes molecular machine systems and medical nanorobots.

Nanomedical Devices

Nanomedicine offers the prospect of powerful new tools for the treatment of human diseases and the augmentation of human biological systems. These tools are called nanomedical devices.Nanodevices are somewhere from 100 to 10,000 times smaller than human cells (FIGURE-1).They are similar in size to large biological molecules such as enzymes and receptors ³. So this offers a unprecedented and paradigm,-changing opportunity to study and interact with normal as well as cancer cell at the molecular and cellular scales and during the earliest stage of cancer process. Because of their small size, nanoscale devices can readily interact with bimolecules on both the surface of cells and inside of cells.

Figure-1: The comparison the size of inorganic nanoparticles with other biological objects

The most elementary nanomedical devices are used to diagnose illness and to repair damages and infections ⁴. The design of the size of nanomedical robots have to include the limit of the capillaries sizes which are located in the capillary beds where in turn the arteries and veins in the body meet. These capillaries have a maximum diameter of 20 microns but an average diameter of 8 microns and the design of nanomedical robots have to be below those sizes because blood cells must flow through those areas as well. Where a blood cell is pliable a nanorobot may not be and it could be possible to get stuck.  The purpose of this review is to magnify some of the nanomedical devices which has been already in use or discovered; their work, structure and applications.

Nanostructured Materials

Nanostructured materials may be defined as those materials whose structural elements like clusters, crystallites or molecules have dimensions in the 1 to 100 nanometer range. The initial medical applications, using nanostructured materials, are already being tested in a wide variety of potential diagnostic and therapeutic areas and are discussed below.

Nanoparticles

Nanoparticles can be engineered to target cancer cells for use in the molecular imaging of a malignant lesion ⁴. Large numbers of nanoparticles are safely entered in to the body and they preferentially bind to the cancer cell, finding the anatomical counter of the lesion and making it visible. These nanoparticles give us the ability to see cells and molecules that we otherwise cannot detect through conventional imaging. Tagged nanoparticles are particles which can track biological events by simultaneously tagging each biological component and become a new class of bioprobes for many biological applications.

Quantum dots

Quantum dots nanocrystals are nanoscale crystals of semiconductors that behave as single “super atoms” .⁵ They are capable of confiring a single electron, or a few, and in which the electrons occupy discrete energy states just as they would in an atom (quantum dots have been called "artificial atoms").

Quantum dots nanocrystals used to tag biological molecules and would have applications in medical diagnostics, targeted therapeutics, and high-throughput drug screening.⁶ They will allow, for the first time, direct imaging of small numbers of dying cells in degenerative eye diseases, and reduce the time frame for testing ocular drugs from 10 years to less than one. They also will greatly enhance imaging during surgical removal of lymph nodes associated with cancerous tumors, thereby improving the prognosis for cancer patients and saving lives while simultaneously reducing the cost and training required for the procedures.

Dendrimers

Dendrimers are precisely defined chemical structures .⁷ The name "dendrimer" is derived from the ancient Greek word "dendron" which means tree, and from the Greek suffix "-mer" which means segment.Dendrimers are manmade molecules having a tree like structures (FIGURE-2).⁸ They are prepared generation by generation in a series of controlled steps that increases the number of small branching molecules around a central core molecule.  Dendrimers measure between two and 20 nanometers across and are branching molecules with the branching beginning at the core. The core generally consists of an amine core, but sugars and other molecules can be used as well. All core molecules share the characteristic of having multiple reaction sites that are identical. The core is mixed with an excess of the first monomer molecule which reacts with all of the core's reaction sites, giving rise to the first branches. This monomer molecule has two distinct reactive groups, one at each end. After one kind of end reacts, the other end will provide reaction sites for the next layer of the shell. 

Figure-2: Detail composition image of Dendrimer

Dendrimers start to be the ideal building block for creating biologically active nanomaterials because of their consistency of structure. The Center for Biologic Nanotechnology has been running tests of functioning biologic nanodevices based on dendrimers especially of nanodevice called anticancer therapeutic nanodevice. These tests have been conducted in vitro on living cells and they confirm that this nanodevice will work as therapeutic agents. It will perform cancer cell recognition, diagnosis of cancer cause, drug delivery, reporting drug levels in tumors and reporting cancer cell death. ⁹

Nanoshells

Nanoshells have a core of silica and a metallic outer layer. These Nanoshells can be linked to antibodies that can recognize tumor cells(PSMA). ⁴Once the cancer cell take them up, by applying a near infra red light that is absorbed by the Nanoshells, it is possible to create intense heat that selectively kills the tumor cells and not the neighboring healthy cells.

Fullerene-based pharmaceuticals

Soluble derivatives of fullerenes such as C60—a soccer ball–shaped arrangement of 60 carbon atoms per molecule—show great promise as pharmaceutical agents. These derivatives, many already in clinical trials, have good biocompatibility and low toxicity even at relatively high dosages. Fullerene compounds may serve as antiviral agents (most notably against human immunodeficiency virus ¹⁰, antibacterial agents (Escherichia coli,¹¹ Streptococcus ,¹² Mycobacterium tuberculosis ¹³, photodynamic anti-tumor ¹⁴ and anticancer  therapies, antioxidants and antiapoptosis agents as treatments for amyotrophic lateral sclerosis  and Parkinson’s disease, and other applications—most being pursued by C Sixty , the leading company in this area.

Medical Nanorobotics Of Tomorrow

In the longer term, perhaps 10 to 20 years from today, the earliest molecular machine systems and nanorobots may join the medical armamentarium, finally giving physicians the most potent tools imaginable to conquer human disease, ill health, and aging. Organic building materials (eg, proteins, polynucleotides) are very good at self-assembly, but the most reliable and high-performance molecular machines may be constructed out of diamondoid materials, the strongest substances known. Many technical challenges must be surmounted before medical nanorobots can become a reality. Building diamondoid nanorobots—the most aggressive objective—will require both massive parallelism in molecular fabrication and assembly processes ¹⁵ and programmable positional assembly including molecularly precise manufacture of diamond structures using molecular feedstock . ^16-18 There will be many species of medical nanodevices. Each species will have different shapes and sizes in order to accomplish different tasks.

Nanoscale Robotic Actuator

A nanoscale actuator is the machine which consists of DNA. It is a structural material as well as a substance driving and controlling the machine's motion. The ring-like structure is formed by two stiff double-stranded DNA regions connected by one short and one long single-stranded DNA section. In just a few years, molecular motors based on this technology could power and control generations of molecular robots. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. It could be used to configure a molecular pegboard or control molecular assemblers. Molecular machines could be used to assemble drugs molecule-by-molecule, and molecular robots may eventually work inside the human body.

Nanotweezers

The first nanotweezer was demonstrated by Philip Kim and Charles Lieber at Harvard University in 1999. It is constructed from two carbon nanotubes which are electrically controlled. The most recent nanotweezer was developed in Scandinavia in 2001 by Boggild et al. ¹⁹  and is based on MEMS electrostatic motor with two cantilevers that bend under an applied voltage. Two very thin probes are grown on the tips of the cantilevers by deposition of carbonaceous material in a SEM and gap between them is as low as 20 nm (FIGURE-3). The researchers hope to produce nanotweezers small enough to grab individual macromolecules and manipulate them in 3-D.

Figure-3: Nanotweezer

Nanosensors and Nanoprobes

The nanosensor equipped with antibody-based bioprobe capable of monitoring biochemicals of single cells was developed by T. Vo-Dinh et al. from Oak Ridge National Laboratory and published in 1998 .²⁰ The preparation of this kind of nanosensor was based on BTP- benzo [a] pyrene tetrol, a biomarker of DNA damage. Following chemical treatment, the medium containing BPT was then aspirated and replaced with standard growth medium, prior to the nanoprobe procedure. Interrogation of single cells for the presence of BPT was carried out using antibody nanoprobes. These antibody nanoprobes were prepared from quartz optical fibers which were pulled in a fiber puller to extremely small dimensions (10-100 nm range). Antibodies to BPT were attached to the tips of the fibers. The fibers were then coated with silver, so as to prevent light from emerging anywhere along the length of the fiber except the tip, where the antibodies are located. The tests done by T. Vo-Dinh et al. command that this kind of nanosensor device would have the capability tomonitor biochemical processes in single cells for chemical and biological warfare early sensing and defense.

Platelets and Clottocytes

Platelets are roughly spheroidal nucleus-free blood cells about 2 microns in diameter with an average bloodstream lifetime of 10 days and a mean blood concentration of ~250,000 cells/mm³. Platelets gather at a site of bleeding, where they are then activated, becoming sticky and clumping together to form a plug that helps seal the blood vessel and stop the bleeding. At the same time, they release substances that help promote clotting.

The artificial mechanical platelet or clottocyte may allow complete hemostasis in as little as ~1 second, even in moderately large wounds .²¹ This response time is on the order of 100-1000 times faster than the natural system. The clottocyte is conceived as a serum oxyglucose-powered spherical nanorobot about 2 microns in diameter containing a fiber mesh that is compactly folded onboard. Upon command from its control computer, the device promptly unfurls its mesh packet in the immediate vicinity of an injured blood vessel. Blood cells are immediately trapped in the overlapping artificial nettings released by multiple neighboring activated clottocytes, and bleeding halts at once.Clottocytes may perform a clotting function that is equivalent in its essentials to that performed by biological platelets -- but at only ~0.01% of the bloodstream concentration of those cells. Hence clottocytes appear to be ~10,000 times more effective as clotting agents than an equal volume of natural platelets.

Microbivore

Nanorobotic phagocytes (artificial white cells) called microbivores ²² could patrol the bloodstream, seeking out and digesting unwanted pathogens including bacteria, viruses, or fungi. During each cycle of nanorobot operation, a target bacterium becomes bound to the surface of the blood borne microbivore like a fly on flypaper (FIGURE-4), via species-specific reversible binding sites. No matter that a bacterium has acquired multiple drug resistance to antibiotics or to any other traditional treatment – the microbivore will eat it anyway, achieving complete clearance of even the most severe blood borne infections in minutes to hours rather than taking weeks to months using present-day antibiotics. Hence microbivores, each 2-3 microns in size, would be up to ~1000 times faster-acting than either unaided natural or antibiotic-assisted biological phagocytic defenses. Related nanorobots could be programmed to recognize and dissolve cancer cells, or to clear circulatory obstructions in a time on the order of minutes, thus quickly rescuing the stroke patient from ischemic damage.²³

Figure-4: Microbivore

Respirocytes

One example of such a future device is the artificial mechanical red blood cell or Respirocytes,²⁴ a blood- borne, spherical, 1-Am diamondoid, 1000-atm–pressure vessel with activepumping powered by endogenous serum glucose, able to deliver 236 times more oxygen to the tissues per unit volume than natural red blood cells and to manage carbonic acidity. The nanorobot is made of 18 billion atoms precisely arranged in a diamondoid pressure tank that can be pumped full of up to 3 billion oxygen (O2) and carbon dioxide (CO2) molecules.²⁵ Later on; these gases can be released from the tank in a controlled manner using the same molecular pumps. Respirocytes mimic the action of the natural hemoglobin-filled red blood cells. Gas concentration sensors on the outside of each device let the nanorobot know when it is time to load O2 and unload O2 (at the lungs), or vice versa (at the tissues). The injection of a 5-mL therapeutic dose of 50% respirocyte saline suspension, a total of 5 trillion individual nanorobots, into the human bloodstream would exactly duplicate the gas-carrying capacity of the patient’s entire 5.4 L of blood. Primary medical applications of respirocytes would include transfusable blood substitution; partial treatment for anemia, perinatal/neonatal, and lung disorders; enhancement of cardiovascular/neurovascular procedures, tumor therapies and diagnostics; prevention of asphyxia; artificial breathing; and a variety of sports, veterinary, battlefield, and other uses.

Conclusion

Over the next couple of years it is widely anticipated that nanotechnology will continue to evolve and expand in many areas of life and science and the achievements of nanotechnology will be applied in medical sciences, including diagnostics, drug delivery systems and patient treatment and the achievements of nanotechnology will be applied in medical sciences. Without losing sight of Feynman’s original long-term vision of medical nanorobotics, nanomedicine today has branched out in hundreds of different directions, each of them embodying the key insight that the ability to structure materials and devices at the molecular scale can bring enormous immediate benefits in the research and practice of medicine. In general, miniaturization of our medical tool will provide more accurate, more controllable, more versatile, more reliable, more cost-effective, and faster approaches to enhancing the quality of human life gives an overview of this rapidly expanding and exciting field. Over the next 5 to 10 years, nanomedicine will address many important medical problems by using nanoscale-structured materials and simple nanodevices that can be manufactured today.

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About Authors:

Geeta Patel is presently working as Lecturer in the department of Pharmaceutics and Pharmaceutical Technology at S. K. Patel college of Pharmaceutical education and research, Kherva, Ganpat University, Mehsana, India. She worked on floating drug delivery system during her post graduation. She has 3 publications in different journals. She further focuses her research activity in the same.
Corresponding Author: E-mail –geekhappy2002@yahoo.co.in

Ritesh Patel is presently working as Lecturer in the department of Pharmaceutics and Pharmaceutical Technology at S. K. Patel college of Pharmaceutical education and research, Kherva, Ganpat University, Mehsana, India. He worked on controlled release dosage form during his post graduation and further focuses his research activity on the advancements in the field.

Dr. Madhabhai Patel is currently Vice-Chancellor of Hemchandrachayra North Gujarat University, Patan, India. He earned his PhD in Pharmaceutics and Pharmaceutical Technology. Dr. Madhabhai Patel has 25 years of academic and research experience. He has 40 national and intentional research papers to his credit. He is an approved PhD guide at Hemchandrachayra North Gujarat University, Patan, India.

R P Patel, H R Patel, G N  Patel and M M Patel

Department of Pharmaceutics & Pharmaceutical Technology, S. K. PatelCollege of Pharmaceutical Education and Research, Ganpat University, Kherva-382711. Gujarat, India.