The credential part of this paper gives the theoretical application of nanodevices in the treatment of cancer. The latest technology for the treatment cancer is the chemotherapic treatment in which drugs of specific composition is given to the patients depending on the biopsy of the tumor from the patient. The main disadvantage of using chemotherapy is that the drug used is not so specific and hence it causes damage to the surrounding healthy cells. It uses MAb, the monoclonal antibodies to locate the affected areas. To make the treatment more specific, we use the nanodevices that use nanosensors to be more specific in application of chemotherapy to the malignant tumors, thereby increasing the safety in usage of chemotherapic drugs. Also the use of biomotors in the nanodevices increases the oxygen content in the surrounding that decreases the hypoxia environment. This is given more importance because the angiogenesis or blood vessel formation for tumors is activated in a low oxygen environment or hypoxia. Also we could make specific compounds that could be carried along with the nanodevices that control the telomerase production, which could serve as a means of controlling cell division.
This paper is only a theoretical analysis given and all the information provided are specifically organized by us with help from a cancer patient, her doctor and a microbiology student. We sincerely thank them for their cooperation with us, for our paper.
INTRODUCTION:
"This technology has the potential to replace existing manufacturing methods for integrated circuits, which may reach their practical limits within the next decade when Moore's Law eventually hits a brick wall,"
- Physicist Bernard Yurke of Bell Labs.
With the introduction of nanotechnology we say we are in for a new invention, but we would rather consider it to be a discovery as it happens in the deepest of human physiology. We knew the concept of this technology from the days of Darwin; even his findings were based on this nanotechnology. There are many evidences for the existence of the so-called concepts of nanotechnology of which some are described in the paper below. This paper gives some of the theoretical applications that could be possible with nanotechnology in the field of bio-medical instrumentation, diagnosed disease treatment possibilities.
What is nanotechnology?
Nano is one billionth of one. Now we have the so-called microprocessors and micromanipulations that would reach the nano level within a few decades, we suppose. Some call this technology to be nanotechnology and some others name if the molecular nanotechnology, to be specific. [2] Whatever we call it, it should let us
1. Get essentially every atom in the right place.
2. Make almost any structure consistent with the laws of physics that we can specify in molecular detail.
3. Have manufacturing costs not greatly exceeding the cost of the required raw materials and energy.
Two more concepts commonly associated with nanotechnology are
1. Positional assembly.
2. Self-replication.
The basic requirements of any technology would be to do any work with greater accuracy and speed. This accuracy needs right programming of the nanocomputers, might be called a nanoprocessor, analogous to the microprocessors that we have now. But at such a small size, the speed required cannot be achieved without large number of nano robots. Also manufacturing of such large number of robots not only requires patience but also is also very tedious. A new concept of self-replication was introduced.
Both positional assembly and self-replication are new in the field of mechanical manufacturing, but are common in our human system. The self-replicating model of a DNA, which arranges the adenine, guanine, cytosine and thiamine with hydrogen bonds in between them, is self-explanatory for both self-replication and positional assembly.
Sci-tech nano verses:
K. Eric Drexler:
1. "If you want to see a nanotechnology machine, look in the mirror."
2. "Assemblers will bring one break through of obvious and basic importance: engineers will use them to shrink the size and cost of computer circuits and speed their operations by enormous factors".
3. "Assemblers will be able to make virtually any thing from common materials with out labor, replacing smoking factories with systems as clean as forests. They will transform technology and economy at their roots, opening a new world of possibilities. They will indeed be engines of abundance".
Howard Aiken said that just six electronic digital computers would satisfy the computing needs of the United States
Feynman said “The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom".
NANO EVIDENCES:
1. In 1990, IBM researchers showed that it is possible to manipulate single atoms. They positioned 35 xenon atoms on the surface of a nickel crystal, using an atomic force microscopy instrument. These positioned atoms spelled out the letters "IBM".
2. Los Alamos and MIT researchers managed to spread a single qubit across three nuclear spins in each molecule of a liquid solution of alanine or trichloroethylene molecules. Spreading out the qubit made it harder to corrupt, allowing researchers to use embarrassment to study interactions between states as an indirect method for analyzing the quantum information.
3. IBM also developed the scanning tunnel microscope and atomic force microscope, which serves as tools for atomic level manipulation.
WHAT IS CANCER?
The human body is made up of many cellular units that worn out regularly. These worn out cells are removed and new cells replaces the old existing cells by a cellular division referred to as mitosis. There are certain control systems that control these dividing mechanisms. Cancerous cells are those cells with boundless dividing capabilities that affect the normal body put up. Cancer begins when there has been a permanent change in the structure of DNA, referred to as the mutation. This change in gene structure takes place in several steps given below. [4]
I. Primary steps:
In this case Safety Systems fails. The cells communicate with each other by receptor organs through the chemotherapic process, i.e. through chemical changes.
Proto-Oncogenes Become Oncogenes:
These messages referred to as the growth factor reaches the adjacent cells and activate the genes known as Proto-Oncogenes, but the case of a mutated gene is referred to as simply Oncogenes which gives message for repeated multiplication of cells, being the main causative of cancerous cell growth.
Tumor Suppressor Genes Stop Working:
This repeated multiplication alone cannot serve to be the cause of cancer. The adjacent cells produce the tumor suppressor activation to inhibit the growth of the cells. At times this might also malfunction.
Cell Cycle Clock Malfunctions:
The cell nucleus contains a collection of interacting proteins that control cell division, called the cell cycle clock that interprets the health of the cell for further processes. If DNA is found damaged then the tumor suppressor gene destroys the cell. In case of cancer, also this gene fails due to one or more mutation processes.
Cells Achieve Immortality:
The normal life span of a cell is controlled within limits by the telomeres, a protector of DNA that reduce in amount during each cell division. At a particular point, the DNA is damaged and the cell is destroyed. But the cancer cells produce telomerase that extends the length of telomeres indefinitely causing an increase in the life span of the cell adding to the tediousness.
B. Secondary steps:
This alone is not enough to produce cancer cause it has to survive a number of other safety mechanisms that prevents the excessive cell growth. Normal cells cannot survive without an extracellular matrix, which is not the case with the cancerous cells.
Tumor Forms:
The tumor is a collection of cells without the aid of extracellular matrix for its survival, which maintains a blood vessel network buy angiogenesis. In case if the tumor is a benign tumor, it would be prevailing only in one part and its surgical removal is also possible. The other is a malignant tumor that serves as the pre-cancer tissue.
Tumors Spread: These malignant tumors spread to the entire region local to it and also affect the nearby regions to form secondary growth or metastases. Also the surface receptor’s resemblances cause the cells to adhere to one another thus increasing the danger of spreading the cancer sells.Thus the cancerous tissue is produced due to mutations in the gene structure causing cancer in the affected regions.
WHAT IS A MAB:
Monoclonal Antibody (MAb), laboratory-produced protein molecule used in medicine to detect pregnancy; diagnose disease, including acquired immune deficiency syndrome (AIDS), hepatitis, and various kinds of cancer; and treat conditions caused by toxins, or poisonous substances, such as snake venom. MAbs best serve medicine as diagnostic tools and treatment aids—that is, in combination with more conventional therapies. They are also used in laboratories to track proteins in experiments.
How is a MAb produced?
An antibody is a Y-shaped protein produced by a type of white blood cell known as a B cell. B cells are produced in the bone marrow of the body and then travel to such organs as the spleen and the lymph nodes. Mature B cells respond to foreign substances called antigens. They then differentiate into plasma cells, which secrete antibodies. Antibodies neutralize or mark antigens for destruction with the help of other cells of the immune system—the system of organs, tissues, cells, and cell products, including antibodies, responsible for ridding the body of disease-causing organisms or substances. Antibodies perform their work by attaching, or binding, to specific parts of antigens. Only antibodies created for a specific antigen can attach to that antigen. Once an antibody is produced, it circulates in the blood; ready to attack its targeted antigen the next time the antigen invades the body. As a result, the blood contains thousands of different types of antibodies.
How MAbs work:
A monoclonal antibody is created in the laboratory by fusing, or joining together, a normal B cell, which normally dies within a few weeks, and a cancerous B cell, which lives indefinitely. This fusion creates a hybrid cell, called a hybridoma, that can live forever and produce an unlimited supply of the antibody secreted by the original, normal B cell. By varying the types of normal B cells used to create hybridomas, scientists can create many different kinds of MAbs, each targeted to a specific antigen.
An ingenious technique was developed that combined the myeloma cell’s (a type of cancer cell) ability to rapidly produce large quantities of the same antibody with the ability of a normal B cell to produce a useful antibody. Normal mouse B cells and mouse myeloma cells were grown together in a laboratory culture. The growing medium included a chemical that would join the membrane of one normal B cell with the membrane of one myeloma cell, creating a B cell hybridoma.
Each hybridoma from the culture when placed it in its own growing medium grew and multiplied at the rapid rate of the original mouse myeloma cell from which it was derived, but all of its daughter cells (the new cells it produced) secreted only the antibody made by the original, normal B cell used to create the hybridoma.
Where MAbs are used:
Today scientists use MAbs to identify and measure minute quantities of hormones, infectious substances, toxins, and other molecules in tissues and fluids. MAbs can also be used to identify malignant cells (cells with abnormal growth) in tissues. In our case to help diagnose cancers hidden in the body, radioactive substances are attached to MAbs that recognize and target cancer cells. These MAbs are then injected into a patient’s body. The MAbs find cancer cells for which they are targeted and bind to them. A special machine that uses film sensitive to radioactivity is used to take an internal picture of the patient’s body. This image reveals any cells to which the MAbs attached, indicating the presence of cancer.
How an anti-cancer drug works:
Anticancer drugs destroy cancer cells by stopping them from growing or dividing at one or more points in their growth cycle. Treatment of patients with metastasized cancer necessitates the use of a therapy that can reach all parts of the body. Chemotherapy, or the administration of cancer-fighting drugs, such as taxol, has proven effective in destroying breast cancer cells that have spread to other organs. Chemotherapy may consist of one or several cytotoxic drugs that kill cells by one or more mechanisms. The goal of chemotherapy is to shrink primary tumors, slow the tumor growth, and kill cancer cells that may have spread (metastasized) to other parts of the body from the original, primary tumor. Chemotherapy kills both cancer and healthy cells.
How chemotherapy works:
It is highly desirable to know what drugs are effective against your particular cancer cells before these toxic agents are systemically administered to your body. Chemosensitivity tests are performed on living specimens of cancer cells to determine the optimal combination of chemotherapy drugs.
Following a healthy analysis of the samples, an Ex-Vivo Apoptotic (EVA) assay taken from the biopsy, the drugs efficiency towards each tumor is identified. Then an assay-directed therapy is recommended for the patient.
How hypoxia induces the growth of cancerous cells:
In response to a low-oxygen environment, cancer cells send out growth signals that result in increased angiogenesis (blood vessel growth into the tumor). Oxygen deprivation not only induces angiogenesis, but also causes cancer cells to express additional survival factors that make them highly resistant to the toxic effects of chemotherapy.
It is an established fact that a low-oxygen environment (hypoxia) promotes tumor growth. If nothing else in this protocol is followed, correcting a hypoxic state could vastly enhance the odds of long-term survival.
The first step in correcting hypoxia is to guard against anemia. Anemia is common in cancer patients, and the result is that less oxygen is delivered to the tumor, that is, hypoxia. Chemotherapy often induces anemia that then exacerbates hypoxia in the tumor.
The best way of evaluating blood oxygen-carrying capacity is to measure hematocrit and hemoglobin levels. Since cancer cells thrive in a hypoxic environment, the cancer patient's hematocrit and hemoglobin should be maintained in the upper one-third range of normal prior to the initiation of chemotherapy.
Rotary Motor:
Biomolecular nanomotor is to be used for the transportation of chemotherapic drugs in our case. It uses the concept of ATP synthesis that serves for two purposes.
The ATPase motor, found in the mitochondrial membrane and in the membrane of many bacteria, consists of a hydrophobic membrane bound F0 portion that enables proton translocation, and a hydrophilic F1 portion that facilitates ATP synthesis and hydrolysis. As protons flow through F0, the γ-subunit of F1 ATPase rotates clockwise and the ATP is synthesized.
Hydrolysis of ATP results in counterclockwise rotation of the gamma subunit and drives the reverse proton flow through a, b, c subunits of the F0 ATPase. This motor has been used to drive nanoscale nickel blades fabricated with specific biocompatible and anti - inflammatory coatings.
What is an ATP?
ATP serves as fuel for basic life functions, such as cell growth and muscle movement. Boyer helped explain the complicated molecular process in which the enzyme, called ATP synthase, processes energy into ATP, which cells then use as fuel. When the body processes nutrients from food or sunlight, chemical energy is released.
The enzyme ATP synthase absorbs that energy, converts it into the fuel-like ATP, and transfers the fuel to any of a number of functions that require it—from the growth of cells to the contraction of muscles to the transmission of nerve messages. [6] ATP synthase transfers energy to ATP molecules by adding a phosphate ion to an adenosine diphosphate (ADP) molecule.Bonding phosphate to ADP produces ATP and makes the molecule more stable, increasing its potential energy. ATP is regarded as a fuel for virtually all processes that require energy in a living organism.
Rotary motion of ATP:
The formation of ATP is tied to the movement of hydrogen ions (positively charged hydrogen atoms). The structure of an ATP synthase molecule is described as a three-sectioned assembly. The lower section is shaped like a wheel and is attached to the membrane of the cell. The rod like second section connects the wheel to the top section, a ball-shaped six-chambered structure. The top section is fixed in place by a thin filament that reaches down and connects to the cell membrane. The top two sections of the enzyme extend into the cell.
Cell respiration (the process in which cells use oxygen to release energy from(sugars) releases hydrogen ions into the liquid surrounding the cells. As long as the concentration of hydrogen ions outside of the cell is greater than that inside, the ions will try to equalize the concentration by moving to the inside of the cell. The ATP synthase molecule provides a way for the ions to move into the cell. The bottom, cylindrical part of the enzyme is located in the cell membrane, and the top two parts extend into the cell.
The ATP synthase is functioned roughly like a three-cylinder engine. It is suggested that the wheel-like chamber at the bottom of the molecule turns as hydrogen ions move through it. The motion from the wheel then turns the rod. The top third of the enzyme is anchored to the cell membrane by the filament, and cannot turn, but it does have three chambers that can expand and
contract. At any one time, one chamber is open and empty, one is loosely closed around a molecule of ADP and a phosphate ion, and one is squeezed tight around a completed ATP molecule. As the middle section of the enzyme rotates, each chamber makes a transition. The open chamber takes in an ADP molecule and a phosphate molecule and closes slightly. The half-closed chamber closes tightly, binding together the ADP and phosphate to form ATP. The closed chamber opens wide, releasing an ATP molecule into the cell.
Function of ATP:
The addition of a phosphate ion molecule to adenosine diphosphate (ADP)results in the formation of adenosine triphosphate (ATP) and water molecule. This increases the oxygen content in the local environment there by decreasing the possibilities of hypoxia and thereby reducing the spread of cancer tumors and the formation of vascular blood vessels or the so-called angiogenesis.
The Nano-sensors:
The ability of medical nanodevices to measure both absolute temperature and changes in temperature is crucial for monitoring in vivo physiological thermoregulatory mechanisms and intracellular energy transactions. Precision thermal sensing is also important within nanoscale devices to provide corrective input for pressure, chemical, and displacement sensors, and to improve the stability of onboard clocks.
The area of chemical microsensors is well developed, and there is increasing research interest in nanoscale chemical sensors "chemosensors" and "biosensors”. The most common nanomedical application of chemical sensors will be to measure the concentration of specific molecules and biopolymers in aqueous solvent -- whether in blood serum, interstitial fluid, or cytosol. This may be accomplished using ordered arrays of receptors or by using sorting rotors to directly count molecular populations in known sample volumes. Chemotactic sensors may be used to sample the chemical composition of surfaces. Pico Newton forces may be applied and must be detected bymedical nanodevices. Pendulum- and cantilever-based sensors may be used to probe nanoscale forces, to monitor the ambient gravitational field, to measure molecular-scale masses to single-proton accuracy, and to discriminate among molecules having different isotopic composition.
NANOSENSORS PRODUCTION THRO’ T4 BACTERIOPHAGE
The recent trends in the field of nanotechnology have been recognized by the developed nations in the world. Even its gaining importance in India
The present technology for the treatment of cancer involves the chemotherapic way that is no way effective. Also the projects under taken in the treatment of cancer using nanotechnology are also not yet implemented effectively.
The present situation has the following ways for treatment of cancer
1. Chemotherapic drugs
2.Immunology
3.Radiotheraphy
The treatment of cancer using nanotechnology uses the following type of sensors
Here we have provided an algorithm for the treatment of the same using the
present technological advancements already implemented.
The algorithm includes
1. Use of Monoclonal Antibodies (MAb) for the detection of cancerous areas, the present radiation detection method.
The present technology for the Single Walled Carbon Nanotubule (SWNT) is either not economical or that it is not very efficient. We have an idea of developing such sensors through this nanotube technology or from genetically coding the T4 bacteriophage that is currently being used to develop FET transistors.
Process that follows are
1.If we use some kind of nanotube that has the characteristics of being attracted by the radiation components then the couple of nanotubes being used would be attracted by these compounds that there would be some displacement in the nanotube coated with the radiation attracted compound.
2.This would change the inter separation distance of the nanotubes there by changing the capacitance in between them.
3.This would directly show the presence of the cancer affected area for the implementation or administration of the chemotherapic drugs through nanosensors.
The recent development of the concept of using T4 bacteriophage for the transistordevelopment is being developed in the MIT, USA
This could be used effectively for the sensor production through
2. Genetically decoding and encoding the T4 bacteriophage to change its characteristics.
IMPLEMENTATION OF NANOTECHNOLOGY IN CANCER TREATMENT:
In this case we could use the nanorobots, specially designed nanodevices that could carry the chemotherapic drugs for the treatment of cancer cells and also to improve the MAb contents in these robots thereby improving the efficiency of the chemotherapy in cancer treatment, which has been a major problem in today’s treatment techniques. Also the use of ATP powered biomotors used for nanodevices create a low hypoxia environment that decreases the danger of spreading of tumor to other regions [3]. The chemotherapic drugs are injected into the patient that along with the MAb are used to identify the affected areas thereby making a localized perception of the cancer tissue. Then the nanosensors used identify the temperature variation in the local environment that detects the specific areas of infection that could be used for application of chemotherapic drugs. The hypoxia is decreased in the local environment, due to the use of bio motors in nanodeviceshelps in controlling the further spreading of tumor. Thus nanotechnology is implemented in the biomedical field for treatment of cancer.
CONCLUSION:
The paper is just a theoretical justification. But the recent advancement in the field of nanotechnology gives the hope of the effective use of this technology in medical field. This paper starts by giving an introduction to nanotechnology and its importance as recognized by various other technocrats. This is the beginning of nanoera and we could expect further improvements such as cure to AIDS using nanotechnology.
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