Monday, January 27, 2020
Gadolinium-based Ferrite Nanoparticles Synthesis
Gadolinium-based Ferrite Nanoparticles Synthesis SAMRAT MAZUMDAR Abstract Cancer is by far one of the most challenging diseases for centuries. In the US, it accounts for over a million deaths annually and is expected to rise in the coming future. Therefore, there is vital need to develop novel strategies, which can help in combating the disease at any level. Metallic nanoparticles present an interesting view, which can function as both therapeutic and diagnostic agents due to their unique properties. The main motive of the proposed work is development of gadolinium based magnetic nanoparticles, followed by their surface functionalization which may improve imaging and targeting outcomes. Doped Gadolinium nanoparticles will be prepared by co-precipitation method for optimum magnetic properties. The synthesized particles will be subjected to functionalization with suitable group for specific target in nature for cancer cells. Eventually, in-vitro studies will be carried out to validate the hyperthermia effect on cancer cells. 1. Introduction Overview Although, it is difficult to define cancer, but in simple terms, it is a group of related diseases which is characterized by uncontrolled cell proliferation and spread, mostly due to loss of control in the cell cycle (Pà ©rez-Herrero and Fernà ¡ndez-Medarde, 2015). The most commonly detected cancers are lung cancer, breast cancer and skin cancer, etc. A variety of factors contributes to the disease progression, such as genetic changes, infections and exposure to carcinogens. In general, cancer is detected/diagnosed by various techniques like, blood tests, X-ray imaging, Computed Tomography (CT) scanning and Endoscopy etc. Conventional treatment strategies include surgery, chemotherapy and radiation therapy. However, they possess numerous limitations especially dose-related side effects and toxicity (Brigger et al., 2002). Currently, researchers are looking towards newer approaches which are selective, non-invasive, non-toxic and effective. These efforts are led to the development o f experimental cancer therapies. These not only improves the curing rate but also, act as a supplement to the conventional therapies. However, it is still early to state that these alternatives can completely replace the existing treatment strategies and its effectiveness in clinical settings, are yet to be determined. Alternative approaches include Gene therapy (Vile et al., 2000), Photodynamic Therapy (PDT) (Dougherty et al., 1998), Hyperthermia (Urano, 1999) ,Targeted Nano-medicines (Xu et al., 2015). Recently, a tremendous amount of research is being carried out in the field of hyperthermia due to encouraging results and its potential for significantly lowered toxicity. Hyperthermia â€Å"Hyperthermia†is a very ancient technique which is now regaining popularity in the field of oncology (Seegenschmiedt and Vernon, 1995). It involves the use of heat energy to elevate the temperature inside a tumour tissue and subsequently kill the cancer cells. The desired temperature range for hyperthermia is 42 °-44 °C which is, greater than the physiological temperature (Wust et al., 2002).There is a variety of factors governing the effectiveness of hyperthermia which includes thermal variables, device characteristics, frequency, current and tumour morphology (Valdagni et al., 1988). At temperatures below 41 °C, blood flow increases while tissue oxygenation increases above 41 °C providing a dual effect against tumour. Once temperatures are increased above 42.5 °C-43 °C, the exposure time can be halved for every 1 °C rise to provide a similar heating efficiency however, excessive heating should be avoided. The heating device used for hyperthermia should be versatile, comfortable as well capable of exhibiting uniform heating patterns. The applied frequencies may range from 5-500 KHz (Lacroix et al., 2008) while a current of about 100-800A might be sufficient for heating. Studies suggest that enlarged tumour with poor vasculature might be more susceptible to heat treatment (Kim et al., 1982). Hyperthermia has a radiosensitizing effect which can be advantageous in combination with radiotherapy since most radioresistant cells are heat sensitive. Classification of Hyperthermia Direct heating/Extracellular method Heat is applied by means of external sources such as thermostatic water bath, infrared sauna and ultrasound. This approach is limited by the presence of biological barriers which is responsible for insulation. Therefore, excess heat is required to achieve the same which can trigger side effects (burns, bleeding). Indirect heating/Intracellular method – Provides a safer and effective means through the injection of nanoparticles followed by their internalization (Ningthoujam et al., 2012).Ex. Magnetic hyperthermia. Mechanism of Hyperthermia Primarily, hyperthermia induce apoptosis, necrosis or autophagy through multiple pathways to cells (Hurwitz and Stauffer, 2014). Reports suggest that it can deliver a higher amount of oxygen into the hypoxic tumour region through changes in blood perfusion. Generally, tumour cells express lower concentration of Heat Shock Proteins (HSP) in comparison to normal cells. Therefore, HSP-peptide complex levels can be increased significantly by the application of hyperthermia, further leading to anti-tumour immunity response (Kobayashi et al., 2014). Magnetic Hyperthermia In order to prevent damage to surrounding healthy tissues from the hyperthermia effect, nanoparticles should be confined to a defined area (tumour region). These are achieved through targeting of nanoparticles by functionalization and application of magnetic fields to specified regions (Baà ±obre-Là ³pez et al., 2013). Metallic magnetic nanoparticles under the influence of oscillating magnetic field undergo a change in magnetic moment attributed to Neel and Brownian fluctuations. These fluctuations are responsible for heat generation through friction, which might be effective in damaging the cancer cells. Limitations of Magnetic Hyperthermia There are technical problems which may act as a barrier towards effective treatment. The two main aspects include uniform heat distribution and desired target temperature (Brusentsova et al., 2005). Treatment might be a failure in case of insufficient thermal dose .There are no well-defined methods used to evaluate the temperature distribution in the target area but, Magnetic Resonance Imaging (MRI) can be used to generate a temperature profile corresponding to hyperthermia. MRI can also be helpful in tracking the release of drug from a formulation (Tashjian et al., 2008). MRI Contrast Agents In the Magnetic Resonance Imaging (MRI) system, most of the magnetic materials (iron based materials) act as T2 contrast agents which give rise to darkened image/negative contrast. Subsequently, this is mode is useful for tracking purpose. However, there are a few disadvantages which limit their usability in clinical settings. Firstly, the dark images accompanied by low signal intensity may often lead to misdiagnosis and secondly, the large magnetic susceptibility can produce MRI artifacts making it increasingly difficult to determine the exact state of the injury or damage. T1 contrast agents (Gadolinium, Manganese) provide a brighter signal, which can be easily observed in the MRI due to their paramagnetic nature which do not disrupt the magnetic homogeneity (Gallo and Long, 2015). Through nanotechnology, it is also possible to simultaneously carry out imaging and drug delivery further, overcoming the limitations posed by the conventional system. 2. Hypothesis/Rationale The paramagnetic Gadolinium exhibits excellent MRI imaging capabilities which can be exploited for several purposes and possesses high magnetic moment. Due to its limited inter-atomic interactions, it is unable produce hyperthermia. We hypothesize that by modifying the properties of gadolinium, it may serve a dual purpose i.e. hyperthermia and imaging. Furthermore, these particles can be tagged with various targeting moieties or loaded with anti-cancer drugs to increase the effectiveness of the therapy. 3. Objectives On the basis of above background, the objectives are as follows. Synthesis and Optimization of Gadolinium-based ferrite nanoparticles. Surface modification of prepared nanoparticles. Folate conjugation to the modified surface coating. Optimization of hyperthermia Characterization and in-vitro studies 4. Plan of work 4.1 Synthesis and Optimization of Gadolinium-based ferrite nanoparticles Gadolinium based ferrite nanoparticles will be synthesised using suitable mechanisms such as chemical co-precipitation method and optimized. 4.2 Surface modification of prepared nanoparticles Surface modification will be carried out by layer by layer (LBL) synthesis. 4.3 Folate conjugation to the modified surface coating Since most cancer cells overexpress folate receptor, folic acid will be conjugated to nanoparticles through amine functionalization. 4.4 Optimization of hyperthermia The process will be optimized by monitoring the parameters affecting it. 4.5 Characterization and in-vitro studies 4.5.1 Characterization The developed nanoparticle will be characterized by the following techniques. Particle size analysis -Zetasizer. Chemical Composition determination-Fourier Transform Infrared Spectroscopy (FTIR), Structural and Crystalline analysis- X-ray Diffraction pattern. Surface Morphology-Scanning Electron Microscopy, Transmission Electron Microscopy. Magnetic Property Testing- Vibrating Sample Magnetometry. 4.5.2 In vitro studies Cytotoxicity studies – MTT Assay will be performed to assess the cytotoxicity and biocompatibility of nanoparticles. In-vitro hyperthermia studies with cancer cell lines Cellular uptake studies- Performed using Transmission electron microscopy and Electron Dispersive X-ray spectroscopy. Magnetic Resonance Imaging studies. 5. Expected Outcomes The developed nanoparticles might exhibit Improved magnetic hyperthermia in comparison to unmodified gadolinium particle. Target localization may be observed through Magnetic Resonance Imaging. 6. Future Prospects Based on in-vitro results in-vivo studies can be performed in animals. This treatment modality can be combined with Photodynamic Therapy and Chemotherapy for better results. 7. References Baà ±obre-Là ³pez, M., Teijeiro, A. Rivas, J. 2013. Magnetic Nanoparticle-Based Hyperthermia For Cancer Treatment. Reports Of Practical Oncology Radiotherapy, 18, 397-400. Brigger, I., Dubernet, C. Couvreur, P. 2002. Nanoparticles In Cancer Therapy And Diagnosis. Advanced Drug Delivery Reviews, 54, 631-651. Brusentsova, T. N., Brusentsov, N. A., Kuznetsov, V. D. Nikiforov, V. N. 2005. Synthesis And Investigation Of Magnetic Properties Of Gd-Substituted Mn–Zn Ferrite Nanoparticles As A Potential Low-T C Agent For Magnetic Fluid Hyperthermia. Journal Of Magnetism And Magnetic Materials, 293, 298-302. Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J. Peng, Q. 1998. Photodynamic Therapy. Journal Of The National Cancer Institute, 90, 889-905. Gallo, J. Long, N. J. 2015. Nanoparticulate Mri Contrast Agents. The Chemistry Of Molecular Imaging, 199-224. Hurwitz, M. Stauffer, P. Hyperthermia, Radiation And Chemotherapy: The Role Of Heat In Multidisciplinary Cancer Care. Seminars In Oncology, 2014. Elsevier, 714-729. Kim, J. H., Hahn, E. W. Ahmed, S. A. 1982. Combination Hyperthermia And Radiation Therapy For Malignant Melanoma. Cancer, 50, 478-482. Kobayashi, T., Kakimi, K., Nakayama, E. Jimbow, K. 2014. Antitumor Immunity By Magnetic Nanoparticle-Mediated Hyperthermia. Nanomedicine, 9, 1715-1726. Lacroix, L. M., Carrey, J. Respaud, M. 2008. A Frequency-Adjustable Electromagnet For Hyperthermia Measurements On Magnetic Nanoparticles. Rev Sci Instrum, 79, 093909. Ningthoujam, R., Vatsa, R., Kumar, A., Pandey, B., Banerjee, S. Tyagi, A. 2012. Functionalized Magnetic Nanoparticles: Concepts, Synthesis And Application In Cancer Hyperthermia. Functionalized Materials, 229-260. Pà ©rez-Herrero, E. Fernà ¡ndez-Medarde, A. 2015. Advanced Targeted Therapies In Cancer: Drug Nanocarriers, The Future Of Chemotherapy. European Journal Of Pharmaceutics And Biopharmaceutics, 93, 52-79. Seegenschmiedt, M. Vernon, C. 1995. A Historical Perspective On Hyperthermia In Oncology. Thermoradiotherapy And Thermochemotherapy. Springer. Tashjian, J. A., Dewhirst, M. W., Needham, D. Viglianti, B. L. 2008. Rationale For And Measurement Of Liposomal Drug Delivery With Hyperthermia Using Non-Invasive Imaging Techniques. International Journal Of Hyperthermia, 24, 79-90. Urano, M. 1999. Invited Review: For The Clinical Application Of Thermochemotherapy Given At Mild Temperatures. International Journal Of Hyperthermia, 15, 79-107. Valdagni, R., Liu, F.-F. Kapp, D. S. 1988. Important Prognostic Factors Influencing Outcome Of Combined Radiation And Hyperthermia. International Journal Of Radiation Oncology* Biology* Physics, 15, 959-972. Vile, R., Russell, S. Lemoine, N. 2000. Cancer Gene Therapy: Hard Lessons And New Courses. Gene Therapy, 7, 2-8. Wust, P., Hildebrandt, B., Sreenivasa, G., Rau, B., Gellermann, J., Riess, H., Felix, R. Schlag, P. 2002. Hyperthermia In Combined Treatment Of Cancer. The Lancet Oncology, 3, 487-497. Xu, X., Ho, W., Zhang, X., Bertrand, N. Farokhzad, O. 2015. Cancer Nanomedicine: From Targeted Delivery To Combination Therapy. Trends In Molecular Medicine, 21, 223-232. 8. Requirements Chemicals Instruments
Sunday, January 19, 2020
Free Essays - Animal Farm :: Animal Farm
ï » ¿Introduction  â€Å"Animal Farm†is a symbolical political satire in which animals take the place of humans. These animals can talk and are just as intelligent as humans. They learn to read and each type of animal a different aspect of humanity. (Ex.: Pigs- Politicians; Horses- Laborers; Sheep- Gullible People; etc. ) This book shows how a government that is set up to serve the people turns against them, just like communism did to the Russian people. Animalism symbolizes communism and the characters symbolize Russian leaders and people of importance. This is a tale with no happy ending.                           Characters                                The Pigs          They symbolize politicians in a stereotypical sense. Some of them lie, cheat,     and steal from the animals they are supposed to serve. They make promises     that are never kept. Propaganda is spread to the animals they are supposed to     represent. Old Major          He is a pig who is very old. He has seen the lifestyle the animals live and is     dissatisfied with it. He creates a government ideology called animalism which     represents communism. He is the Karl Marx of this world. Napoleon          He is a large, fierce looking Berkshire boar, who is not much of a talker. He     uses animalism only to increase his power and the dogs to terrorize the other     animals. Napoleon symbolizes the dictator Joseph Stalin in this world. Snowball          He is a pig that fights with Napoleon over the power on the farm. He is a very     energetic, eloquent speaking, brilliant leader who organizes the defense of the     farm. Napoleons jealousness of him makes him try to kill Snowball. Snowball     flees the area and every misfortune in Animal Farm after that is blamed on     him. He represents Leon Trotsky in this story. Squealor          He is a short, fat, twinkle eyed pig who is a brilliant talker. He justifies the     horrible actions of Napoleon and most of the animals buy into it. He has a sly,     persuasive air to him. This is why he is head of Napoleon’s propaganda plan.  Boxer          He is a large, very powerful horse who is not too bright. He buys into     animalism and works the hardest on the farm. He saves the farm on multiple     occasions and declared a national hero. After he gets too sick to work     Napoleon secretly sells him to a glue factory. Boxer symbolizes the hard     working Russian class that Stalin abused for his own benefit. Mollie          She is a mare who abandons Animal Farm for sugar and ribbons at the human
Saturday, January 11, 2020
Phesant Analysis
Sylvia Plath The poem, , has a theme, which is talking about a complex relationship of Plath. Plath uses pheasant as a symbol for representing her complicating complex. This poem also conveys of realism of nature, which reflects to the reality of a human being. This poem consists of 8 identical stanzas. Each stanza contains 3 lines. It has an irregular rhyme scheme and an imperfect rhyme. Plath starts off the poem directly. The first word of the poem, â€Å"You†, reveals that Plath is having a conversation or a negotiation with someone.The first 2 lines in the poem depict a serious but quiet atmosphere with slight grudges. Thus, Plath has shown a tone of pleading, reflected by the phrase â€Å"Do not kill it†. Then, the poem comes up with a run-on verse. It reveals Plath is emphasizing the idea here. â€Å"The jut of that odd, dark head†obviously is portraying the appearance of a pheasant. It also illustrates that Plath sees a pheasant, whose head is staying upo n the uncut grass, is pacing around. Plath also sets a foil to the peaceful atmosphere by the slow pace of the pheasant.There is a great dichotomy with the first line of the poem. The ambiance has been changed abruptly. The following lines show that Plath is talking with somebody softly, not owing to forgiveness, it is because Plath seems like suffering from hell pain and weak to convey words. â€Å"I am not mystical†, the first line in third stanza, indicates that Plath is connecting to spiritual aspect of thing, perhaps like God. And then, Plath is referring to the pheasant. Plath â€Å"thought it had a spirit†and â€Å"in its element†. The concept of Plath is that the pheasant belongs to the nature, as it is an element of it.Plath implicitly conveys that if the peasant need to end up its life, it should be caused naturally but not by any man-cause. That’s what Plath is halting somebody from killing the pheasant. In the forth stanza, Plath perhaps depi cts that pheasant is a paramount, wonderful creature in Plath’s mindset. â€Å"Kingliness†portrays the pheasant is living proudly in the nature. There are landmarks by the pheasant hither and thither, illustrated by the word phrase â€Å"tail-track†. In addition, the fifth stanza is a resonation of the forth stanza, which emphasize the gorgeous aspect of the pheasant.The word â€Å"wonder†echoes with the word â€Å"kingliness†. Plath also projects that pheasant is unique and special and can stand out to catch her attention among other birds. The â€Å"pallor†of the pheasant is charming and captivating. Afterward, Plath comes up with a question and a statement at the same time. â€Å"Is it its rareness, then? It is rare. †this line reveals the pheasant has occupied an important position of Plath. The sixth stanza is a respond to the fifth stanza. Plath expresses that even there is tons of pheasant; it is still â€Å"a fine thingâ € .The exclamation used highlight Plath’s impression. In the seventh stanza, Plath is complimenting the pheasant. â€Å"Good shape†, â€Å"vivid†are words that praising the pheasant. Thus, Plath uses metaphor to compares pheasant as Zeus, the greatest god in Greece mythology, indicated by the word â€Å"cornucopia†. Thus, the metaphor is followed by a simile, â€Å"brown as a leaf, and loud†. Perhaps Plath is portraying the colour, the size and the movement of the pheasant. In the last stanza, Plath illustrates the pheasant is enjoying under the sunshine â€Å"in the narcissi†.There is a hidden meaning here. The word narcissus appears in the name of a disease, narcissistic personality disorder. Perhaps Plath chooses this plant for precise presentation. And as a result, Plath chooses to â€Å"let be, let be†, reveals that Plath is giving up. Throughout the entire poem, Plath uses pheasant to represent a series of themes, like love, relationship and realism. Perhaps Plath uses the pheasant for presenting herself as a weak woman without any defence. And pheasant is also the one, which is defenceless. It reflects the role of Plath.If Plath is using pheasant as a metaphor to describe she, then the compliments in the poem belongs to her. That means she is praising herself. In Plath’s opinion, she is a precious woman as diamonds that everyone should cherish and treat her well when getting along with her. Plath should be paramount and be complimented all the time and she thinks that she can receive the glory. Unfortunately, things do not go on as Plath anticipated. Plath is pleading someone not to sabotage her relationship and love. If not, Plath will simply possess nothing.On the surface, everything goes logically but owing to the existence of â€Å"narcissi†, we may guess perhaps Plath has been suffering from narcissistic personality disorder. She is psychologically unhealthy and does not possess a c lear mind. She is confused and begins absurd right now. But what we can still predict that Plath has illusions is owing to bad and nasty treatment. In conclusion, the poem pheasant illustrates a serious atmosphere but elegant description on the surface. Implicitly, this poem shows the madness of Plath derive from complex love and relationships and innate human evil – deceiving.
Friday, January 3, 2020
The Model Of Racial Equality - 888 Words
In certainty, the model of racial equality has not always been performed, nor has it been fully accomplished in the world. This is because the acceptance in racial equality has been said to â€Å"counter†deeply rooted beliefs in racial inequality and political, legal, and customary practices of racial discrimination and oppression. Therefore, racial equality is stated in antiracist philosophy and in antiracist political mobilization. With this said, as citizens, are we still equal? The answer to that question is â€Å"no†. The world is living in Orwellian times where citizens are equal, but some citizens are more equal than others. While some agree, there are many groups that are pushing for reform and equality, such as Take Back Our Republic, By The People, and Common Cause: Holding Power Accountable. Now that the facts are said, we must ask â€Å"how did we become so unequal?†Over time, big corporations, racial groups, and corruption in government have been advocating inequality for the minority. Some people are filled with wrong ideas and beliefs that attack those in the minority group, especially people of color. Franklin said, â€Å"almost from the beginning of their national history, people have been relentless, at times ruthless, in their pursuit of equality.†Nearly fifty years ago, Martin Luther King Jr. delivered his â€Å"I Have a Dream’ speech, a clarion call for the end of racial discrimination in the United States. 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