Sunday, October 02, 2005

NanoTechnology for Cancer Treatment

NANOTECHNOLOGY

-ADVANCE CANCER DIAGNOSIS PREVENTION & TREATMENT

….GO SMALL FOR BIG ADVANCESHEALTH AND HUMAN SERVICES



BY

G.ARUNSHORI (FINAL YEAR EEE) - arunshori_143@yahoo.com

S.R.RENKANATHAN (FINAL YEAR EEE) - rensr_32@rediffmail.com

SARANATHAN COLLEGE OF ENGINEERING


CONTENTS

Ø Introduction

Ø Developing Cancer Nano-Technology Plan

Ø What Is Nano-Technology

Ø Preparing Nano Particles

v Nano Bullets Using Gold And Silica

v Using RNA As Building Blocks

Ø Diagnostics using Nano-Technology

Ø Types of Nano Particles

v Uni-functional Nano Particles

v Multi-functional Nano Particles

ABSTRACT

NA N O T E C H N O L O G Y A N D CA N C E R


To help meet the goal of eliminating death and suffering from cancer by 2015, the National Cancer Institute is engaged in efforts to harness the power of nano -technology to radically change the way we diagnose, image, and treat cancer. Already, NCI programs have supported research on novel nanodevices capable of one or more clinically important functions, including detecting cancer at its earliest stages, pinpointing its location within the body, delivering anticancer drugs specifically to malignant cells, and determining if these drugs are killing malignant cells. As these nanodevices are evaluated in clinical trials, researchers envision that nanotechnology will serve as multifunctional tools that will not only be used with any number of diagnostic and therapeutic agents.

Nanotechnology will change the very foundation of cancer diagnosis, treatment, and prevention.

INTRODUCTION:

The advent of nanotechnology in cancer research couldn’t have come at a more

opportune time. The vast knowledge of cancer genomics and proteomics emerging as

a result of the Human Genome Project is providing critically important details of how

underpinnings of cancer. However, scientists lack the technological innovations to turn promising molecular discoveries into benefits for cancer patients. It is here that nanotechnology can play a pivotal role, providing the technological power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.

To harness the potential of nanotechnology in cancer, NCI is seeking broad scientific input to provide direction to research and engineering applications.

In doing so, NCI will develop a Cancer Nanotechnology Plan. Drafted with input from experts in both cancer research and nanotechnology, the Plan will guide NCI in supporting the interdisciplinary efforts needed to turn the promise of nanotechnology and the postgenomics revolution in knowledge into dramatic gains in our ability to diagnose, treat, and prevent cancer. Though this quest is near its beginning, the following pages highlight some of the significant advances that have already occurred from bridging the interface between modern molecular biology and nanotechnology.

DE V E L O P I N G A CA N C E R--NA N O T E C H N O L O G Y PL A N

NCI’s Cancer Nanotechnology Plan will provide critical support for the held though extramural projects, intramural programs, and a new Nanotechnology Standardization Laboratory. This latter facility will develop important standards for nanotechnological constructs and devices that will enable researchers to develop cross-functional platforms that will serve multiple purposes. The laboratory will be a centralized characterization laboratory capable of generating technical data that will assist researchers in choosing which of the many promising nanoscale devices they might want to use for a particular clinical or research application. In addition, this new laboratory will facilitate the development of data to support regulatory sciences for the translation of nanotechnology into clinical applications.

The six major challenge areas of emphasis include:

1. Prevention and Control of Cancer

Developing nanoscale devices that can deliver cancer

prevention agents

Designing multicomponent anticancer vaccines using

nanoscale delivery vehicles

2. Early Detection and Proteomics

Creating implantable, biofouling-indifferent molecular

sensors that can detect cancer-associated biomarkers that

can be collected for ex vivo analysis or analyzed in situ,

with the results being transmitted via wireless technology

to the physician

Developing “smart” collection platforms for

simultaneous mass spectroscopic analysis of multiple

cancer-associated markers

3. Imaging Diagnostics

Designing “smart” injectable, targeted contrast agents

that improve the resolution of cancer to the single cell level

Engineering nanoscale devices capable of addressing

the biological and evolutionary diversity of the multiple

cancer cells that make up a tumor within an individual

4. Multifunctional Therapeutics

Developing nanoscale devices that integrate diagnostic

and therapeutic functions

Creating “smart” therapeutic devices that can control the

spatial and temporal release of therapeutic agents while

monitoring the effectiveness of these agents

5. Quality of Life Enhancement in Cancer Care

Designing nanoscale devices that can optimally deliver

medications for treating conditions that may arise over

time with chronic anticancer therapy, including pain,

nausea, loss of appetite, depression, and difficulty breathing

6. Inter disciplinary Training

Coordinating efforts to provide cross-training in

molecular and systems biology to nanotechnology

engineers and in nanotechnology to cancer researchers

Creating new interdisciplinary coursework/degree

programs to train a new generation of researchers

skilled in both cancer biology and nanotechnology

WHAT IS NA N O T E C H N O L O G Y ?

Nanotechnology refers to the interactions of cellular and molecular components and engineered materials—typically clusters of atoms, molecules, and molecular fragments—at the most elemental level of biology. Such nanoscale objects—typically, though not exclusively, with dimensions smaller than 100 nanometers—can be useful by themselves or as part of larger devices containing multiple nanoscale objects. At the nanoscale, the physical, chemical, and biological properties of materials differ fundamentally and often unexpectedly from those of the corresponding bulk material because the quantum mechanical properties of atomic interactions are influenced by material variations on the nanometer scale. In fact, by creating nanometer scale structures, it is possible to control fundamental characteristics of a material, including its melting point, magnetic properties, and even color, without changing the material’s chemical composition.

Nanoscale devices and nanoscale components of larger devices are of the same size as biological entities. They are smaller than human cells (10,000 to 20,000 nanometers

in diameter) and organelles and similar in size to large

Noninvasive access to the interior of a living cell affords the opportunity for unprecedented gains on both clinical and basic research frontiers.

HOW TO PREPARE NANO PARTICLES?

Nano-bullet for non-invasive treatment of cancers

Virginia Commonwealth University physicists , working with one of the most precious materials on Earth – gold -- and with one of the most common – sand -- have created a so-called “nano-bullet” that targets tumors and may help scientists develop non-invasive cancer treatments.

The scientists found that when gold particles are reduced to a few nano-meters -- just billionths of a meter -- they become highly reactive and readily bind to silica clusters, allowing the cluster to absorb infrared light and create enough heat to potentially kill cancer tumors. Silica is the main element in sand.

Scientists examined the electronic structure and bonding properties of gold and silica. and observed a dramatic change in the physical properties of both when their sizes were reduced to two or three nano-meters. The gold atoms readily accept electrons, and the new gold coating on the silicon atoms completely changes the charge distribution and electronic structure of the silica cluster. The gold coating on silica results in a significant change in the optical gap, which is a critical factor in determining how light, is absorbed.

“The advantage of using smaller particles is that they can be inserted into any part of the human body and treat cancer cells in their infancy.” Both gold and silica have been used in bio-materials .The measured energy gap confirm that these clusters can absorb infrared radiation

RNA COULD FORM BUILDING BLOCKS FOR NANO MEDICINES-----
By encouraging ribonucleic acid (RNA) molecules to self-assemble into 3-D shapes resembling spirals, triangles, rods and hairpins, the group has found what could be a method of constructing lattices on which to build complex microscopic machines. From such RNA blocks, the group has already constructed arrays that are several micrometers in diameter – still microscopically small, but exciting because manipulating controllable structures of this size from nano particles is one of nanotechnology's main goals. Moreover we can control the construction of three-dimensional arrays made from RNA blocks of different shapes and sizes.
Nanotechnologists, built microscopic devices with sizes that are best measured in nanometers – or billionths of a meter. Because nature routinely creates nano-sized structures for living things, many researchers are turning to biology for their inspiration of construction tools. Biology builds beautiful nano scale structures on this basis

Organisms are built in large part of three main types of building blocks: proteins, DNA and RNA. Of the three, perhaps least investigated and understood is RNA, a molecular cousin to the DNA that stores genetic blueprints within our cells' nuclei. RNA typically receives less attention than other substances from many nanotechnologists, but the molecule has distinct advantages.
"RNA combines the advantages of both DNA and proteins, and forms versatile structures that are easy to produce, manipulate.
Since discovery of a novel RNA plays a vital role in a microscopic "motor" used by thebacterialvirusphi29."By designing sets of matching RNA molecules, we can program RNA building blocks to bind to each other in precisely defined ways, We can get them to form the nano-shapes we want.
From the small shapes that RNA can form – hoops, triangles and so forth – larger, more elaborate structures can in turn be constructed, such as rods gathered into spindly, many-pronged bundles. These structures could theoretically form the scaffolding on which other components, such as nano-sized transistors, wires or sensors, could be mounted.
Because these RNA structures can be engineered to put themselves together, they could be useful to industrial and medical specialists.

NA N O T E C H N O L O G Y A N D DI A G N O S T I C S:











Today, cancer-related nanotechnology research is proceeding on two main fronts: laboratory-based diagnostics and in vivo diagnostics and therapeutics. Nanoscale devices designed for laboratory use rely on many of the methods developed to construct computer chips. For example, 1–2 nanometer-wide wires built on a micron-scale silicon grid can be coated with monoclonal antibodies directed against various tumor markers. With minimal sample preparation, substrate binding to even a small number of antibodies produces a measurable change in the device’s conductivity, leading to a 100-fold increase in sensitivity over current diagnostic techniques.

Nanoscale cantilevers, microscopic, flexible beams resembling a row of diving boards, are built using semiconductor lithographic techniques. These can be coated with molecules capable of binding specific substrates—DNA complementary to a specific gene sequence, for example. Such micron-sized devices, comprising many nanometer-sized cantilevers, can detect single molecules of DNA or protein.

Researchers have also been developing a wide variety of nanoscale particles to serve as diagnostic platform devices .For example, DNA-labeled magnetic nanobeads have the potential to serve as a versatile foundation for detecting virtually any protein or nucleic acid with far more sensitivity than is possible with conventional methods now in use. If this proves to be a general property of such systems, nano particles-based diagnostics could provide the means of turning even the rest biomarkers into useful diagnostic or prognostic indicator .

Nano scale devices have the potential to radically change cancer therapy for the better and to dramatically increase the number of highly effective therapeutic agents. Nanoscale constructs should serve as customizable ,targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells, which would greatly reduce or eliminate the often unpalatable side effect that accompany many current cancer therapies. Already , research has shown that nano scale delivery devices, such as dendrimers (spherical, branched polymers), silica-coated micelles, ceramic nanoparticles, and cross-linked liposomes ,can be targeted to cancer cells. This is done by attaching monoclonal antibodies or cell-surface receptor ligands that bind specially to molecules found on the surfaces of cancer cells , such as the high-affinity folate receptor and luteinizing hormone releasing hormone (LH-RH), or molecules unique to endothelial cells that become co-opted by malignant cells,

such as the integrin in αvβv. Once they reach their target, the nanoparticles are rapidly taken into cells. As efforts in proteomics and genomics uncover other molecules unique to cancer cells, targeted nanoparticles could become the method of choice for delivering anticancer drugs directly to tumor cells and their supporting endothelial cells. Eventually, it should be possible to mix and match anticancer drugs

with any one of a number of nanotechnology-based delivery vehicles and targeting agents, giving researchers the opportunity to fine-tune therapeutic properties without needing to discover new bioactive molecules.



On an equally unconventional front, efforts are focused on constructing robust “smart” nanostructures that will eventually be capable of detecting malignant cells in vivo, pinpointing their location in the body, killing the cells, and reporting back that their payload has done its job. The operative principles driving these current efforts are modularity and multifunctional, i.e., creating functional building blocks that can be snapped together and muddied to meet the particular demands of a given clinical situation. A good example from the biological world is a virus capsule, made from a limited set of proteins, each with a specific chemical functionality, that comes together to create a multifunctional Nano delivery vehicle for genetic material. In fact, at least one research group is using the empty RNA virus capsules from cowpea mosaic virus and .cookhouse virus as potential nanodevices. The premise is that 60 copies of coat protein that assemble into a functional virus capsule offer a wide range of chemical functionality that could be put to use to attach homing molecules—such as monoclonal antibodies or cancer cell-speci.c receptor antagonists, and reporter molecules—such as magnetic resonance imaging (MRI) contrast agents, to the capsule surface, and to load therapeutic agents inside the capsule.

While such work with naturally existing nanostructures is promising, chemists and engineers have already made substantial progress turning synthetic materials into multifunctional nanodevices. Dendrimers, 1- to 10-nanometer spherical polymers of uniform molecular weight made from branched monomers, are proving particularly adept at providing multifunctional modularity. In one elegant demonstration, investigators attached folate—which targets the high-af.nity folate receptor found on some malignant cells, the indicator before skin, and either of the anticancer drugs methotrexate or paclitaxel to a single dendrimer. Both in vitro and in vivo experiments showed that this nanodevice delivered its therapeutic payload specifically to folate receptor-positive cells while simultaneously labeling these cells for fluorescent detection. Subsequent work, in which a fluorescent indicator of cell death was linked to the dendrimer, provided evidence that the therapeutic compound was not only delivered to its target cell but also produced the desired effect. Already, some dendrimer-based constructs are making their way toward clinical trials for treating a variety of cancers.

Such multifunctional nanodevices, sometimes referred to as nanoclinics, also enable new types of therapeutic approaches or broader application of existing approaches to killing malignant cells.

Once these so-called nanoclinics have been taken up by the target cell, they can not only be imaged using MRI, but can also be turned into molecular-scale thermal scalpels applying a rapidly oscillating magnetic field causes the entrapped Fe2O3 molecules to become hot enough to kill the cell. The critical factor operating here is that nanoparticles can entrap 10,000 or more Fe2O3 molecules, providing both enhanced sensitivity for detection and enough thermal mass to destroy the cell.


Photosynthesis is used in photodynamic therapy, in which light is used to generate reactive oxygen locally within tumors, have also been entrapped in targeted nanodevices. The next step in this work is to also entrap a light-generating system,

such as the luciferin-luciferase pair, in such a way as to trigger light production only after the nanoparticles have been taken up by a targeted cell. If successful, such an approach would greatly extend the usefulness of photodynamic therapy to include treatment of tumors deep within the body. Such multifunctional nanodevices hold out the possibility of radically changing the practice of oncology, perhaps providing the means to survey the body for the first signs of cancer and deliver effective therapeutics during the earliest stages of the disease. Certainly, researchers envision a day when a smart nanodevice will be able to fingerprint a particular cancer and dispense the correct drug at the proper time in a malignant cell’s life cycle, making individualized medicine a reality at the cellular level.

platform technologies that can be mixed and matched with new targeting agents that will come from large-scale proteomics programs already in action and therapeutics both old and new. Accomplishing this goal, however, will require that engineers and biologists work hand in hand to combine the best of both of their worlds in the .ght against cancer.

ADVANTAGES:

ü Cancer cells are easily detected in less time.

ü Less side effects

ü Treatment takes less time.

ü Advance method is diagnosis, treatment, prevention can be done in single step using single device.

CONCLUSION:

Researches are going on in different basis on NANO DEVICES and NANO ROBOTS. It is sure that within a decade Nano technology will be the aid through which cancer will be detected and cured. It is already proved experimentally in the National Cancer Institute that nano devices can be used for delivering guided drugs and nano robots can be used for treating the defected cells.

*******THE END*******