Programmable Nanodevices for Biomedical Application: From Science Fiction to Reality

Chandan Adhikari ,  Assistant Professor, Lovely Professional University, India

In 1960 a science fiction picture named ‘Fantastic Voyage’ was released with the storyline that A Nano-submarine was containing a group of scientists traveling through the bloodletting inside the body of a scientist to prevent his brain tumor. Almost sixty years later we are very close to making that fiction into true. Nanomedicine, a newly emerging branch, become very popular among the various group of scientists nowadays.

Suppose a patient is suffering from a brain tumor, and immediate surgery is required to keep him alive, but the location of the tumor is very critical and normal surgery available to date will not guaranty the success. Now, what if doctors can enter into the patients’ body to perform this critical surgery or destroy the tumor which is otherwise impossible. What if we can control the team of the doctors from the outside of the patient’s body to help them to go to the right place of the disease site and give them proper signal to operate with 100 percent precision and success to ensure that the patient will be alive. Although it looks a wonderful storyline of Hollywood science fiction movies (Fantastic Voyage was such a kind of movie which shows the ultimate use of nanotechnology and miniaturises a team of doctors to the nanoscale and sends them to patients' body to perform a critical surgery) but we have achieved very close to this reality through the application of nanorobotics with the help of nanotechnology over the last few decades. Nanotechnology is the 21st century's most astounding and promising technology which aims to miniaturise the materials to the nanometer scale. A nanometer is one-billionth of a meter, more easy to understand that if we divide a human hair into 80000 parts, then one part is one nanometer, too small to be seen with a conventional laboratory microscope. It is at this size scale - about 100 nanometers or less - that biological molecules and structures inside living cells operate.

Application of nanotechnology to biomedical sciences imply manufacturing of materials and devices designed to interact with the body at molecular levels with a high degree of specificity.  Nanomedicine can provide cure to many life-threatening diseases within the next few years like cancer, cardiovascular disease, neurological (especially neurodegenerative) diseases.  Nanomedicine which is a smart combination of medical science and nanotechnology become very popular term nowadays among various research groups over the whole world and rapidly attracting the scientist throughout the globe due to its amazing possibility and future application in the diverse field ofmedical science. One of the most promising applications of nanomedicine is targeted chemotherapeutic drug delivery which has found practical applications in recent times and worth billion-dollar market in the pharma industry. The pharma companies are investing millions of dollars for the development of nanomedicine for various types ofdrug delivery system preferably for chemotherapeutics, and there is an inherent reason behind it.

To bring a drug into the market from its synthesis, it takes almost 15 years with a cost of more than $500 million with thousands of manpower.  After this tremendous effort and investment, most of the drugs do not enter into the market as they suffer from high side effects, poor adsorption, poor solubility, high drug dosing, minimum efficiency, and uncontrolled, nonspecific delivery with high cytotoxicity and all these factors limit their uses. In case of chemotherapeutic drugs, the concern is more because most of the anticancer drugs are highly toxic to the healthy cells and damage the healthy cells along with the cancer cells that results in side effects for the patients. The adverse problems can be overcome, and toxicity can be minimised if the drugs are delivered through a vehicle that delivers the drugs precisely on demand. To achieve the precise and targeted delivery of the drugs, we need a Drug Delivery System (DDS) that delivers the drugs to the target cells in a controlled manner without affecting the healthy cells. There are numerous types of drug delivery systems developed both from organic molecules and inorganic materials in the past few decades. Few practical examples can be shown to justify the potent use of nano-vehicles or nanodevices to solve many problems of biomedical science. One of the most useful drugs to cure many cancers is Doxorubicin, but it suffers from high side effects and cytotoxicity which hinders its wide applications. To overcome these problems Doxorubicin was encapsulated in lipid vesicles (also known as Liposome) which reduce its many side effects and improves its efficacy and the drug sold as Doxil which is the first FDA approved nano-Drug Delivery System and the most successful drug delivery system till now. There are many drugs, e.g., Camptothecin, Topotecan, Ellipticine, etc. which can be improved by changing their delivery using a nano-delivery system. Even the patent for Doxil is also expired, but till now no generic Doxil is available, so the filed is open and versatile, and Pharma companies can look for the possibilities.

If this is one side of the application of nanotechnology in biomedical science, the other side, which is less explored and has found very little or no practical application is programmable nanodevices whichmay be one of the solutions to solve many problems like multisite drug delivery, on-demand drug delivery, targeted on-demand drug delivery, etc. and in recent times many research groups as well as pharma companies throughout the globe are looking into that possibility. People are also thinking about the designing programmable nano-surgical instruments which can be inserted into patients’ body and can be controlled from outside to achieve 100% success.Few results are already showing its bright future. Nanorobots which is a combination of robotics and nanotechnology is one of the possible routes to achieve this fiction like reality. But there are many hurdles to design a nanorobot for biomedical applications.

The first one is the stability and lifetime of the nanorobot as soon as it enters to the human body and comes into contact with the body fluids, the fate of the robot inside the vein decided by various factors. What will happen to the nanobots during the travel through the blood stream which is like a high-speed river with lots of enemies like white blood cells which are ready to destroy any foreign members, how the nanobots will survive the turbulence and waves of the blood stream, how will they protect themselves from the blood pressure? Let's say scientists have solved these problems, but still, our body has its own defense mechanism which will not allow any foreign particles and as soon as the nanobots are identified they will be destroyed by antibodies which are like armed forces of our body. Let again assume that scientists have solved these problems also, but still, there is another level of difficulty which is the microenvironment of the targeted cite which if unknown to the nanobots may destroy them or nanobots may not function properly. So, if we consider our body a highly secured multistoried building and the disease site as a secured vault then the task of the nanobots is like enter to this secured multistoried house with unknown threat and multiple security system and thengoing into the secured vault to do the job and then come back through all the hurdles without destroying the house. So,it is like a perfect heist to be performed which needs a smart expert team [in this case it is nanobots] and proper planning and without proper planning it is impossible to achieve this. So first we have to design the nanobots and have to decorate the surface of this Nanobots withappropriate defense mechanismaccording to the problems so that it survives through all the hurdles. For examples, we can modify its surface (using biomolecules found in our body) such a way which will behave like a familiar particle and will not be destroyed by the body's security system. It is like you are entering the house by taking makeup of any member of the house, so the security will not cause any harm to you. But to understand which type of modification is required one need to do stringent biological studies both in vivo and in vitro.

Until now we have discussed only the possible harmful effects ofa human body to the nanobots, but there is another side of it which is the biocompatibility and toxicity of the nanobots itself. If nanobots are not biocompatible and toxic so they will not be useful anymore. So, the next step is to make them biocompatible and reduce the toxicity level to the threshold limit. There are many ways to do it. One of the approaches could beby surface modification of the nanomaterials with biocompatible molecules, and there are multiple options for it.

The reader may find this discussion very interesting, but the main point is missingtill now, will you able to find the missing point. The main question to design nanorobots with programmable capability for biomedical application is to choose the right materials. So, which elements will be your best choice, the elements must have the conducting properties unless we cannot get any electronic properties, it must be biocompatible, it must be miniaturised to nano-dimension, and a huge amount of data must be available to researchers. One of such materials can be silica because of its semiconducting properties (look at the emerging field of micro and nanochip technology), tunable size and shape (nano-dimension materials can be easily prepared;you can look at the rapidly decreasing size of electronics devices over the last few years) tunable pore size (the pore actually carry and release the cargo molecules)low toxicity,  high biocompatibility,  easy cargo loading, high loading capacity, and ability to release the encapsulated guest under different external stimuli.

Until now the scientist has achieved such kind of programmable nanodevices which can carry the drug molecules and release according to the demand on multiple disease site, but the study is limited invitro only which shows more research is required in this field.So, we can hope for the day shortly when nano-doctors will perform their job at the disease site with a 100% success rate. The programmable nanobots will remain intact inside the patient’s body and will release the drug according to the condition of the disease and requirement for the dose. The day is not so far when a team of nanobots will enter to the human body and will perform their job based on the command given by the control room outside from the body. Let’s hope for the best and a futuristic medical technology which is emerging quite fast and will change all the medical theories and concept known so far. Hope that many more pharma and robotics company will invest on amazing side of this nanotechnology and we will see a new era of 21st centuries medical science.

References:

1.    Sensors, 2008, 8, 2932-2958; doi: 10.3390/s8052932
2.    Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol, 2013, 5, 544-568, doi: 10.1002/wnan.1236.
3.    Nanoscale. 2013, 5, 1259-1272, doi: 10.1039/c2nr32554c.
4.    Molecular pharmaceutics, 2015, 12, 3158-3166, 10.1021/acs.molpharmaceut.5b00043
5.    Journal of Drug Delivery Science and Technology, 2018, 303-314, doi: 10.1016/j.jddst.2018.03.020

Chandan Adhikari

Chandan Adhikari is currently working as Assistant Professor at Lovely Professional University, India. He completed Masters from IIT Hyderabad, India and Ph.D. from IIT Indore, India with specialisation in ‘Applications of Nano-materials in Biomedical Science’ [Published 13 Research article]. He also worked at IACS Kolkata as National Post-Doctoral Fellow [2017-2018].

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