Nanorobots: Novel Technology for Cancer Therapy | Triple Helix ...

Figure 1. Nanorobot sensors, molecular sorting rotors, fins, and propellers. Courtesy A. Cavalcanti

Human knowledge, with all its growth and development, is still in its initial stages of finding efficient ways to treat cancer. The elevated number of cancer patients puts cancer treatment amongst the top priority of scientific research facilities. The advent of nanotechnology opens new windows that promise effective ways in locating the chemical sources, tracking them, controlling the cancerous cells, and finally terminating them.

Cancer is the unusual and uncontrolled growth of cells that have the ability to migrate to other locations and spread out. Cancerous cells replicate faster than healthy cells, causing strain in the nutrient supply and in the elimination of metabolic waste products. Due to the fast growth of the cancer cells, the healthy cells cannot compete for adequate nutrients, and will eventually be replaced by tumor cells. After a tumor develops, only the cells in the outer surface will have access to nutrients, so the inner ones will perish. At some point the tumor growth rate will reach a steady state where the rate of cell death will equal the rate of cell proliferation, and stay in steady state until the tumor finds better access to the circulatory system [2]. A decisive factor in determining the patient?s chance of survival is how early the cancerous cells are detected.

An important aspect in cancer therapy is the development of a targeted drug delivery system that decreases the toxic side effects of chemotherapy. The current conventional method in treating cancer involves inserting catheters to allow for chemotherapy, to reduce the amount of cancer present, and then to surgically remove the tumors, followed by more chemotherapy and radiation sessions [2]. However, the delivery of the drug is not localized, so even the healthy cells that normally divide rapidly will be targeted by the treatment. These factors emphasize the need to deploy a technology that can provide molecular level agents that will act autonomously inside the human body. These agents have to be capable of identifying the cancerous cells in their initial stages and transmitting the appropriate signals to an external device where the physician can read and analyze the information. Or they would have to be equipped with drug delivery and drug injection systems to perform targeted delivery. A technology in possession of these assets could only be sought out in the nano world. Nanorobots navigate as bloodborne devices, so they can be utilized to help diagnose the cancer in its early stages and participate in smart drug delivery [3].

A nanorobot capable of performing these tasks needs to have certain tools and technologies, such as sensors, actuators, data transmitters, power supply, etc. As a result, the hardware architecture for nanorobots in cancer therapy has evolved into an innovative field of engineering, where the goal is to fit the most capable of sensors and actuators within the least amount of space possible.

The main manufacturing technique in early nanorobot sensor design takes advantage of the high precision technology of CMOS (Complementary Metal Oxide Semiconductor) VLSI (Very Large Scale Integration) system design [4]. CMOS-based biosensors use nanowires as material for their circuit assembly. They can detect minimal chemical changes [5], such as E-cadherin and beta-catenin gradients, which can serve as chemical targets for detection of early metastatic phases [6].

To help propel the nanorobot inside the body, an actuator needs to be implemented in the design. An actuator is a device that serves as an engine and helps the nanorobot move. There are different kinds of actuators that use electromagnetic, piezoelectric, electrostatic, and electrothermal sources, depending on where they will be applied [6]. Besides the actuator itself, the continuous available source of power is the key to upholding the successful operation of the nanorobot. Nanorobots can be powered by ambient energy, the motion-based interaction within the bloodstream, which could be utilized to generate kinetic energy [7]. Remote inductive powering in the order of milliwatts, which has been used for RFID (Radio Frequency Identification Device) and biomedical implanted devices [8] could also be used to wirelessly supply energy to nanorobots [9].

Nanorobots could be used to tag the cancerous cells, so that the surgeon could efficiently and precisely remove the tumor. Two methods have been used to target the nanoparticles to tumor sites, which are commonly known as active and passive targeting.? In active targeting, the nanoparticle is linked to tumor-specific ligands [10], whereas passive targeting relies on the mere similarity in size of the nanoparticle with the unique properties of the tumor?s vasculature [11].

Quantum dots could be conjugated to tumor-specific ligands in order to label the cancer cells for the surgeon to perform a more accurate surgery. Quantum dots are semiconductor nanocrystals that owe their fluorescence emission to excited electrons [12]. They have an inorganic elemental core (e.g., cadmium, mercury) with a surrounding metal shell, and demonstrate intrinsic fluorescent spectra depending on their size and chemical composition [13]. Once quantum dots bind to the substrate of interest, they emit a certain wavelength that could be easily detected. Quantum dots can be prepared in a way so that they can be excited with a single light source, but emit at different wavelengths, allowing for independent labeling. Gao et al, for example, were able to locate three different quantum dots with the illumination of a single light source, after they injected them into three different locations inside a mouse [14] (Fig. 2).

Figure 2. ?Multicolor quantum dot (QD) capability of QD imaging in live animals. Approximately 1 to 2 million in each color were injected subcutaneously at 3 adjacent locations on a host animal. Images were obtained with tungsten or mercury lamp excitation? (15). Fair use claimed.

Perhaps the most important benefit of using nanorobots to treat cancer is the smart drug delivery. The major cancer treatment cycle for chemotherapy can take up to several months, with two-week radiation cycles needed to treat small tumors [16]. In these sessions, even the healthy cells surrounding the tumor are exposed to radiation, which brings numerous chemotherapy side effects. Nanorobots will be able to detect the cancerous cells within one week [17], and perform localized drug delivery once they encounter the tumor cells. As nanotechnology further shrinks the size of these nanorobots while adding on to their technical capacity, it is not far from reality that these agents will soon replace chemotherapy. These smart robots will browse through the human body, search for the tumor cells, and either label the target cells and transmit the proper signals to the surgeon, or deliver the drug preinstalled in them, and thus eliminate the tumor.

The success of this technology, just like any other research, lies in the translation of these achievements from the laboratory to a clinical setting.? National Cancer Institute (NCI) Alliance investigators continue to observe promising results from several therapeutic and diagnostic nano-agents which are in phase I of clinical trials [18].

There is nothing dangerous about manipulating the size of objects to nano scales. However, as with any new technology, the safety of nanoparticles needs to be continuously tested. Some safety-related issues, such as the high reactivity or magnetic properties of nanoparticles, have raised concerns. For example, recently there have been debates about the toxicity of carbon nanotubes (CNTs) regarding their association with tissue damage in animals [19]. Nonetheless, there have also been major studies showing no toxic side effects associated with nanoparticles [19]. To insure the safety of these nanoparticles, an intramural branch of the NCI Alliance, the Nanotechnology Characterization Laboratory (NCL), is in close collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST). To date, the groups have evaluated more than 125 different nanoparticles intended for medical applications [19].? ?Certainly, the nanoparticles used as drug carriers for chemotherapeutics are much less toxic than the drugs they carry, and are designed to carry drugs safely to tumors without harming organs and healthy tissue? [19].

References:

1. Cavalcanti A., ?Assembly Automation with Evolutionary Nanorobots and Sensor-Based Control applied to Nanomedicine?, IEEE Transactions on Nanotechnology, Vol. 2, no. 2, pp. 82-87, June 2003.
2. Lisa Brannon-Peppas , James O. Blanchette. ?Nanoparticle and targeted systems for cancer therapy?.? Adv Drug Deliver Rev. 2004; 5(11): 1649-1659.
3. Freitas R A Jr. ?Pharmacytes: an ideal vehicle for targeted drug delivery?. Nanoscience and Nanotechnology. 2006; 6: 2769-75.
4. Lambert B and Weitekamp D P. ?Mechanical sensors of electromagnetic fields?. US Patent Specification 6835926, 2004.
5. A. S. G. Curtis, M. Dalby, N. Gadegaard. ?Cell signaling arising from nanotopography: implications for nanomedical devices?.? Nanomedicine J., Future Medicine. 2006; 1(1): 67-72.
6. Janda E, Nevolo M. Lehmann K, Downward J, Beug H and Grieco M. ?Raf plus TGF beta-dependent EMT is initiated by endocytosis and lysosomal degradation of E-cadherin?. Nat. Oncogene. 2006; 25: 117-30.
7. Roundy S, Wright P K and Rabaey J M. ?Energy Scavenging for Wireless Sensor Networks?. Berlin, Springer; 2006.
8. Ghovanloo M and Najafi K. ?Awide-band frequency-shift keying wireless link for inductively powered biomedical implants?.? IEEE Trans. Circuits Syst. I. 2004; 51(12): 2374-83.
9. Takeuchi S and Shimoyama I. ?Selective drive of electrostatic actuators using remote inductive powering?. Sensor Actuators A: physical. 2002; 95(2-3): 269-73.
10. Akerman ME, Chan WC, Laakkonen P, Bhatia SN, Ruoslahti, E. ?Nanocrystal targeting in vivo?. Proc Natl Acad Sci USA. 2002; 99: 12617?12621.
11. Vasir JK, Labhasetwar V. ?Targeted drug delivery in cancer therapy?. Technol Cancer Res Treat. 2005; 4: 363?374.
12. Alper J. ?Shining a light on cancer research?. NCI Alliance for Nanotechnology in Cancer USA, 2005.
13. Akerman ME, et al. ?Nanocrystal targeting in vivo?, Proc Natl Acad Sci USA. 2002; 99: 12617-21.
14. Gao X, Cui Y, Levenson RM, Chung LW, Nie S. ?In vivo cancer targeting and imaging with semiconductor quantum dots?. Nat Biotechnol. 2004; 22: 969?976.
15. Alex G. Cuenca et al. ?Emerging Implications of Nanotechnology on Cancer Diagnostics and Therapeutics?. Cancer. 2006; 107(3): 459-66.
16. ?sterlind K. ?Chemotherapy in small cell lung cancer?. Eur. Resp. J. 2001; 18: 1026-43.
17. Adriano Cavalcanti et al. ?Nanorobot architecture for medical target identification?. Nanotechnology. 2008; 19(1).
18. National Cancer Institute (NCI) [www.cancer.gov]. [cited 2011 Jul 14]. Available from: http://nano.cancer.gov/learn/now/clinical-trials.asp.
19. National Cancer Institute (NCI) [www.cancer.gov]. [cited 2011 Jul 14]. Available from: http://nano.cancer.gov/learn/now/safety.asp.

Kasra?Naftchi-Ardebili is a fourth-year student at the University of Chicago majoring in physics and biochemistry. Join The Triple Helix Online on?Facebook and follow us on?Twitter.

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