Contents

LIST OF TABLES AND FIGURES ....................................................................................................................... 2 

ACKNOWLEDGEMENT .................................................................................................................................. 3 

INTRODUCTION............................................................................................................................................ 4 

WHY NANO‐PARTICLES? ............................................................................................................................... 5 

WHY DO WE NEED IMAGING ..................................................................................................................................... 6  ........................................................................................................................................................................... 6 WHAT ARE VARIOUS IMAGINING TECHNIQUES ............................................................................................................... 6 HOW DO THEY DO IT ................................................................................................................................................ 7 

WHAT A CHEMICAL ENGINEER GO TO DO WITH IT?? .................................................................................... 8 

DRIVING FORCE FOR NANOPARTICLES IN HUMAN BODY .............................................................................. 9 

[SEE: RHEOLOGY OF HUMAN BLOOD, NEAR AND AT ZERO FLOW] ................................................................................................... 9 

IMPORTANT NANOPARTICLES AND THEIR ROLE IN IMAGING OF CANCER CELLS .......................................... 10 

GOLD NANOPARTICLES : ......................................................................................................................................... 10 HOW ARE THEY USED IN IMAGING OF CANCER CELLS .................................................................................................... 10 

QUANTUM DOTS ....................................................................................................................................... 11 

ROLE OF NANO PARTICLES IN CONTRAST FOR MIR AND OTHER EQUIPMENT'S ............................................ 13 

CONCLUSION ............................................................................................................................................. 14 

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List of Tables and Figures

Fig. 1 6

Fig. 2 10

Fig. 3 11

Fig. 4 11

Fig. 5 12

Fig. 6 12

Fig. 7 12

Fig. 8 13

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Acknowledgement

It gives me great pleasure to present my Project report on “Manufacturing of Liquid

Insulators” No work, big or small, has ever been done without the contributions of others. We

would like to express our deepest gratitude towards Mr Chetan Patel (Assistant Professor at

Chemical Engineering Department, SVNIT) who gave us his valuable suggestions, motivation

and the direction to proceed at every stage. And we also offer our sincere gratitude all those

who extended their kind and valuable guidance, indispensable help and inspiration at times in

appreciation. Lastly we would like to thank Dept. of Chemical Engineering, SVNIT.

Thanks

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Introduction

It has been almost decades since the “war on cancer” was declared. It is now generally

believed that personalized medicine is the future for cancer patient management. Possessing unprecedented potential for early detection, accurate diagnosis, and

personalized treatment of cancer, nanoparticles have been extensively studied over the last decade. In this report, I will try to summarize the current state-of-the-art nanoparticles in biomedical applications targeting cancer. Multi- functionality nanoparticle-based agents.

Targeting ligands, imaging labels, therapeutic Drugs, and other. And the Role of Chemical Engineers in this field and the promise that it holds for future.

Nanotechnology, an interdisciplinary field involving chemistry, engineering, biology, and medicine and has great potential for early detection, accurate diagnosis, and treatment of cancer. Nanoparticles (<100 nm in size) are comparable to large biological molecules. With the size of about 100 to 10,000 times smaller than human cells, these nanoparticles can offer unprecedented interactions with biomolecules both on the surface of and inside the cells, which may revolutionize cancer diagnosis and treatment.

Nanoparticles can be engineered as Nano platforms for effective and targeted delivery of drugs and imaging labels by overcoming the many biological, biophysical, and biomedical barriers. The Behaviour of nanoparticles is quite different from their constituent elements which possess engineering as well as physical challenges which must be addressed before this study can be expanded further. Over the last decade, there have been many rigorous development and experimentation in this field of nanotechnology worldwide and have produced quite a large pool of information on the subject that can be exploited. The well-studied nanoparticles include quantum dots, Carbon nanotubes paramagnetic nanoparticles, liposomes and gold nanoparticles. Though there are many others.

The advantages of state-of-the-art Nano devices and other nano technology over traditional assay methods are obvious even though several barriers exist.

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Why Nano-Particles?

There are many different nanoparticles: liposomes, dendrimers, carbon nanotubes, quantum dots, magnetic nanoparticles, etc. Their size lies in the range of 1–100 nm, a size regime that gives rise to new, unique physical and chemical properties. These properties, together with the high surface-to-volume ratio of nanoparticles and their size being comparable to those of biomolecules make nanomaterial a powerful tool for imaging, diagnosis and therapy. Not only this Nanoparticles can be engineered as nano-platforms for effective and targeted delivery of drugs and imaging labels by overcoming the many biological, biophysical, and biomedical barriers. New optical, electronic, magnetic and structural properties of nanometre scale offer significant opportunities for in vivo applications. Use of Nano technologies in may enable the following possibilities:

High surface area makes them chemical reactivity and enable them to connect with additional functional materials.

Quantum-confinement effects, impart better electronic, magnetic, and optical properties

Cancer detection at the earliest stages.

Assessment of therapeutic efficacy at real time.

Targeting and bypassing of the biological barriers to deliver directly to cancer tissues

Identification of molecular changes in cells that further become cancerous.

However, several barriers exist in use of nanotechnology, among which are :

• The biocompatibility.

• Tumour targeting efficiency.

• Acute and chronic toxicity.

• Ability to escape the lymph nodes/spleen.

• Cost-effectiveness.

Other advantages include multicolour optimization, absence of photo bleaching and other possible degradations, high quantum yield and possibility to simultaneously identification of multiple markers. Nanomaterial can provide control of the therapeutic effect, better bioavailability, prevention of

drug deactivation before it reaches a tumour.

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Why do we Need Imaging

Various imaging techniques provide and edge over conventional methods of

diagnosis as:

1) Imaging techniques provide us with real time visualization of cellular.

Functions and living organisms and and related molecular interactions.

2) They are non- invasive and provide visual data which are far more superior to

mathematical data.

3) They help to determine the target for drug delivery systems thus, surpasses

any guess work.

4) Help to monitor prognosis of cancer cells, neurodegenerative diseases or any

other diseased cells.

5) Help in obtaining biological information and functions at preclinical stages.

6) Lastly, they help to understand the life cycle, effect and others aspect of

cancerous cell or other threat to help design better and more improved drug

delivery systems.

What are various imagining techniques

1. Computed X-ray tomography (CT). 2. Optical imaging. 3. Magnetic resonance imaging (MRI). 4. Positron emission tomography (PET). 5. Single-photon-emission computed tomography (SPECT). 6. Ultrasound.

Fig.1: Comparison of images with and 

without contrast in CT scan [2]

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Most presently available imaging probes and contrast agents are chemical or radioactive agents. Inorganic nanometre-sized colloidal particles (nanoparticles) have been extensively used in many imaging. Most of these equipment rely on ability of nanoparticles to be able to carry Anti-EGFR’s which can combine to cancer cell to produce better images. Then using either of the above mentioned machines the images can be obtained. (See: Raman Effect, Fluorescent microscopy)

How do they do it

All most all imagining techniques need a contrasting agent that help to differentiate affected cell/ tissues from healthy ones and this is where nano technology comes in to play. Most presently available imaging probes and contrast agents are chemical or radioactive agents. However, the tremendous recent advances in nanotechnology have led to the development of new types of probes based on nanoparticles.

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What a Chemical Engineer got to do with it??

Foremost function of a chemical engineering lies in the development of techniques for the synthesis of these nanoparticles. We understand the behavior of nano particles and also have a knowledge about their various properties.

[2]We as engineers can help in determining the success of magnetic drug delivery. It quantifies the competition between particle movements (convection) by blood flow versus particle diffusion in the blood, and is defined as:

Also in finding diffusion coefficients for the endothelium membrane and the surrounding tissue, are defined as:

Where DB is the particle diffusion in blood caused by thermal fluctuations, DS is the additional diffusion caused by collision with blood cells, DM is the diffusion in the endothelial, and DT is the particle diffusion in surrounding tissue (all in units m2/s).

Thus, we can provide a better insight in development of such particles. Nanotech in imaging is not only important in bio-chemistry or bio-medical but have a tremendous usage in catalysis (especially in zeolites) and mechanical operation in chemical industry.

Search for better nano-particles for bio-medical field can or will revolutionize chemical technology

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Driving Force for Nanoparticles in Human Body [See: RHEOLOGY OF HUMAN BLOOD, NEAR AND AT ZERO FLOW]

A Homogeneous disperse system under flow, there are, at the walls of blood vessels fewer

particles than in the bulk of bloodstream because of the "excluded volume” effect. Hence

there exists at the wall a "slip" film of lower viscosity than that of the bulk. And if the walls

are at the same time smooth particles specially white blood cells stick to wall and then flow

this phenomenon is called “migration “.

The same principle is utilize for flow of [3] nano particles decorate with ligands that will

recognize the tumour. Once drugs enter the bloodstream the nanoparticles tend to remain

well suspended in the blood in order to reach the tumour.

As a Chemical engineer our aims is to apply engineering principles to tease out this

mechanism for development of nanoparticle imaging and drug delivery.

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Important Nanoparticles and their Role in imaging

of cancer Cells

Gold nanoparticles :

There are many subtypes of gold nanoparticles based on the size, shape, and physical properties.

Fig: 2: Various Gold Nano Particles [3]

Synthesis:

1. Sphere (2 -100 nm): by controlled reduction of an aqueous HAuCl4 solution using different reducing agents under varying conditions.

2. Rods : using template method, based on the electrochemical deposition of gold within the pores of nonporous polycarbonate or alumina template membranes

3. Shell: Seeded growth technique for coating the silica nanoparticles with gold in an aqueous environment.

4. Cages: Via galvanic replacement reaction between truncated silver nano cubes and aqueous HAuCl4.

5. SERS: Various optical techniques are utilized in aid with above mentioned techniques.

How are they used in imaging of cancer Cells

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Gold nano particles have ability to absorb and scatter light an effect also called Raman Scattering. Now, cancer cells have a receptor called EGFR all over the surface which can be used as target for detection of such cells. When Nano particles are embedded with anti-EGFR which are attracted to EGFR and thus help attachment to cells. Once attached the nano particles reflect light from the cancer cells.

Thus, making them distinguishable from healthy cells.

Fig: 3: Gold Nano particles under different imaging techniques [4]

Fig.4: Multiplexed in vivo Raman imaging using SERS nanoparticles [5]

Quantum Dots

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Quantum Dots (QDs) are 2-8 nm semiconductor Nano crystals typically composed of cadmium selenide (CdSe). They have a spherical shape with dimensions <100 nm. Their small size results in the physical confinement of conduction band electrons. A Change of solvent, precursor or temperature can be used to tune the size of QDs during their synthesis from organometallic precursors.

The synthesis of quantum dots with a water-soluble and paramagnetic micellular coating as a molecular imaging probe for both fluorescence microscopy and MRI.

The toxicity of QDs is one of the main concerns in medical applications. For protection of the body against metal poisoning, QD surfaces have to be covered with a passivation agent, typically zinc sulphide (ZnS) or cadmium sulphide (CdS). Different biocompatible agents, such as proteins, sugars, or other bio-recognition molecules are often added to these outer-surfaces.

A significant increase in the effective particle size caused by these add-ons, may badly affect renal elimination of QD materials. Changing their size also changes the light that they reflect and it is this ability that is used in Cancer Cell Imaging.

Fig.5: Quantum Dot Structure in bio-medicine 

field [6]

Fig.6: Absorption and emission Spectra [7]

Fig 7: Visualization of distinct cancer cell in a using quantum dots (QDs) for

imaging [8]

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Role of nano particles in Contrast for MIR and

other Equipment's

1. Manganese oxide nanoparticles have been used as contrast agent for magnetic resonance imaging (MRI), allowing researchers to see inside living brains in the same detail as dissected tissue under a microscope.

2. QD’s as a contrasting agent in fluorescence microscopy help to visualize cell in various Color under different wavelength of light.

3. Contrast agents for X-ray and CT show contrasting effects according to the electron-density difference, and they produce direct contrast effects on their positions. This electron density can be controlled via use of nano particles thus providing a better contrast.

Conventional contrast agents include paramagnetic transition metal ions (such as Mn2+ and Fe3+) or rare-earth chelates (such as Gd3+). But there are drawbacks to using these metals. 'Free manganese ions substitute for calcium, causing cardio-vascular toxicity [9]

Fig. 8: The structure of MRI contrast agent 

based on nanoparticles [10]

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Conclusion

Targeting ligands, imaging labels, therapeutic drugs, and many other functional moieties can all be integrated into the nanoparticle to allow for targeted molecular imaging and molecular therapy of cancer.

Nanoparticle are unique in a sense because of their intriguing optical properties which can be exploited for both imaging and therapeutic applications.

The future of Nano medicine lies in multifunctional Nano platforms which combine both therapeutic components and multimodality imaging.

The ultimate goal is that nanoparticle-based agents can allow for efficient, specific in vivo delivery of drugs without systemic toxicity, and the dose delivered as well as the therapeutic efficacy can be accurately measured non-invasively over time.

Much remains to be done before this can be a clinical reality and many factors need to be optimized simultaneously for the best clinical outcome.

The most promising applications of nanoparticle based agents will be in cardiovascular medicine, and in oncology.

We as Chemical engineer are left with too much to explore and study in these nano- particles.

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References

[1]:http://www.learningradiology.com/archives04/COW%20119-AVM%20of%20Brain/avmcorrect.htm (11th dec-12) [2] : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057021/ (11th Dec)

[3] http://www.dovepress.com/getfile.php?fileID=3421 (9th Dec 12)

[4] http://www.pharmainfo.net/reviews/quantum-dots-novel-technique-drug-delivery-and-therapy (9th Dec 12)

[5] http://www.pharmainfo.net/reviews/quantum-dots-novel-technique-drug-delivery-and-therapy (9th Dec 12)

[6,7] http://www.pharmainfo.net/reviews/quantum-dots-novel-technique-drug-delivery-and-therapy (11th Dec 12) [8] http://www.pharmainfo.net/reviews/quantum-dots-novel-technique-drug-delivery-and-therapy (11th Dec 12) [9]: http://www.rsc.org/chemistryworld/News/2007/April/06040701.asp (9th Dec 12)

[10] : http://nanomag.ucsd.edu/wp-content/uploads/2011/12/MRI-contrast-particles.pdf (9th Dec 12)