Nanotheranostic Approach for Cancer Therapy and Imaging

Nanotheranostic Approach for Cancer Therapy and Imaging HER 2 conjugated multifunctional cubic phase nanoparticles (CPNPs): A nanotheranostic approach for cancer therapy and imaging Abstract Recently, cubic phase nanoparticulate systems are used as attractive vehicle in drug delivery research due to sustained release of both hydrophilic and hydrophobic drugs for cancer therapy. Currently, theranostic approach also emerged as frontier proposition for cancer therapeutics and diagnostics for better cancer management. Moreover, targeted drug delivery systems may be applied to increase the therapeutic index of the drugs and imaging agents at the targeted site. With an aim to develop a theranostic nanoformulation capable of drug delivery and imaging in a single shot, in the present study, HER 2 antibody conjugated cubic phase nanoparticles (CPNPs) were prepared by entrapping rapamycin (as a model anticancer drug) and QD 605 (as an imaging agent). The physicochemical characterisations of CPNPs were performed by different techniques. The antibody conjugated to CPNPs was confirmed by FT-IR and 1H NMR spectral analysis. In vitro studies were performed and demonstrated that, HER 2 conjugated rapamycin loaded CPNPs showed improved therapeutic efficacy than that of native rapamycin and rapamycin loaded CPNPs in HER 2 positive SKBr 3 cell line following enhanced cellular uptake through receptor mediated endocytosis. The molecular mechanisms of the particulate system on different signalling pathways were evaluated by western blot analysis. Further, the use of above system as an imaging modality was elucidated through optical imaging under in vitro system. Thus, these multifunctional CPNPs can be used as an effective targeted drug delivery system for cancer therapy and diagnosis in coming future. Introduction The life threatening disease cancer now becomes a challenge for survival worldwide due to its high mortality rate. So to achieve a better treatment modality, researchers are trying to develop new methodology for better management of cancer. Though chemotherapeutic agents are effective to some extent, however, clinical applications of these anticancer drugs are remained as a major problem due to their hydrophobic nature, low accessibility at the targeted site and dose limiting toxicity. With cancer tissues these drugs also affect the normal tissues with detrimental side effects [1, 2]. To overcome the lack of tumor specificity of cancer chemotherapy and diagnosis, till date nanomedicinal approaches have emerged as a hope for better therapeutics in cancer by using different nanocarriers like micelles, liposomes, solid lipid nanoparticles and nanoparticles consisting of biodegradable polymers etc. These approaches ultimately enhance the therapeutic potentiality of the drug in a sustaine d, controlled and targeted manner for longer period of time reducing the lethal side effects arose due to the drugs [3-5]. Recently, due to the capability to solubilise the hydrophilic, hydrophobic and amphiphilic molecules, cubic phase nanoparticulate systems are used as attractive vehicle in controlled drug delivery research [6]. In this regard, glyceryl monooleate (GMO) a synthetic lipid amphiphilic molecule approved by food and drug administration is known to form different lyotropic liquid crystalline phases depending upon water content. The cubic phase formed from GMO is a three dimensional network of curved lipid bilayers separated by intricate network of congruent water channels, now has been used for controlled drug delivery of different water soluble and insoluble drugs in the form of CPNPs [7, 8]. The use of surfactants may modulate the phase behaviour by controlling the shape and size of the nanoparticles which is an important parameter to cross different physiological barriers. In this current scenario, usually the surfactants like poly vinyl alcohol (PVA), tween 80, Pluronic F-127, Pluronic F-68, polysorbate 80 and vitamin-E TPGS etc are used as stabilisers in clinical studies to increase the therapeutic efficacy of the drug at the tumor site. In this regard, Barauskas et al have demonstrated that using Pluronic F-127 as a stabilising agent, stable aqueous nanoparticle dispersions may be obtained from the cubic phase of GMO [9]. Also it is shown that Pluronic F-127 through passive targeting can enhance the transportation of the drug towards cancerous tissues by inhibiting the drug efflux transporters [10]. Similarly, a well known natural polymer vitamin-E TPGS due to its biocompatible nature and excellent emulsifier in nanotechnology, is used for lipid-based drug delivery formulations. Moreover, also it can be used as an absorption enhancer and bioavailability promoter and facilitates the nanoparticles for carrying the drugs through gastrointestinal barrier. Apart from the above properties, recently vitamin-E TPGS is reported to inhibit p-gp pump effectively [11-13]. Recently, rapamycin and it analogs has been shown to inhibit the cancer cell growth obtained from breast cancer, pancreatic cancer, prostate cancer, lung cancer, rehabdomyosarcoma, glioblastoma, neuroblastoma, osteosarcoma, leukemia and ÃŽ ²-cell lymphoma. Rapamycin is a cytostatic agent and it shows its function by arresting the cells in G1 phase of cell cycle. The antitumor activity of rapamycin is found by blocking mTOR pathway, proposed to be an important target for treatment of cancer due to its involvement in tumorigenesis and angiogenesis on aberrant activation [14-16]. In spite of having potent anticancer effects of rapamycin, the clinical application is restricted due to its low bioavailability and hydrophobic nature [17]. In this milieu, nowadays different nanoparticulate systems are being used by different group of researchers to improve the therapeutic efficacy of rapamycin with a smaller dose for longer period of time in a controlled manner [2, 18]. Targeted drug deliver y vehicles are now emerged for improvement of treatment modality of the therapeutic agents and/or imaging agents strictly localising its pharmacological activity at the site of action through active targeting [1]. The surfaces of nanoparticles are decorated with peripheral ligands which bind specifically to the receptors those are over expressed in cancer cells arbitrating ligand-receptor interaction. Human epidermal growth factor receptor-2 (HER 2), tyrosine kinase transmembrane receptor are highly expressed in different types of cancers like breast cancer, pancreatic cancer, gastric cancer, glioblastoma, ovarian cancer etc. Humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin) was approved by U.S. Food and Drug Administration for clinical trials and it exclusively binds to HER 2 receptors preventing the cell growth in breast cancers. Targeted drug delivery with the help of mAb has drawn attention as an alternative approach for antibody mediated drug delivery of the chemotherapeutic agents for effective clinical translation [19, 20]. Nowadays optical imaging has been explored in biomedical research due to its high sensitivity, cost effectiveness, portability and lack of radiation and it shows marvellous implication by providing information for both in vitro and in vivo studies [21, 22]. The development of light emitting semiconductor nanocrystals known as quantum dots (QDs) have emerged as one of the most exciting interface of nanotechnology due to its unique optical and chemical properties over organic dyes. The unique properties of these QDs lead powerfully to study in molecular, cellular and in vivo imaging with advantages including narrow, symmetrical and tunable emission spectra according to their size and material composition, broad absorption spectra, high quantum yield, extremely photostable, more brightness and resistance to chemical degradation [23, 24]. In this study, we have formulated a theranostic nanocarrier for targeted drug delivery and imaging in treatment of cancer. Here, preparation and characterisation of HER 2 conjugated rapamycin and QD 605 loaded CPNPs based on GMO was done by blending pluronic F-127, vitamin-E TPGS, TPGS-HER 2 as a targeting moiety. Therapeutic evaluation of our formulated CPNPs was performed by taking both HER 2 positive and negative cell line through different in vitro experiments. Results confirmed that HER 2 conjugated rapamycin loaded CPNPs due to their higher uptake through receptor mediated endocytosis were more effective than that of unconjugated CPNPs and native drug treated case. Furthermore, in vitro cellular imaging study of formulated multifunctional CPNPs was validated by confocal microscopy and the results suggested that this multifunctional particulate system can act as a single bullet capable of obtaining a new concept for better therapeutics and diagnostics in cancer.

Business Research Terms and Concepts Essay

Understanding Business Research Terms and Concepts: Part 3 A. Determine which level of measurement— nominal, ordinal, interval, or ratio—is used in the following examples. 1. The Association of Accountants is conducting a survey to determine the ranking of the top 100 accounting firms in the world. Ordinal 2. How many years did it take you to earn your college degree? Ratio 3. On a questionnaire which asks for gender, males are coded as 1 and females are coded as 2. Nominal 4. Respondents are asked to rate a list of high-tech companies as excellent, good, fair, or poor in terms of their service delivery. Ordinal 5. Cereal brands are arranged in an ordered sequence in which an equal interval exists between each point. Interval 6. Jake Locker averages 350 yards per game passing. Interval 7. The length of time it takes the winner of a marathon to cross the finish line. Ratio 8. Students are asked to rank computer manufacturers. Ordinal 9. The brand of charge card used by a customer. Nominal B. Which sampling method—simple random, systematic, stratified, cluster, convenience, judgment, quota, or snowball—is most appropriate for the following examples? Explain why. 1. The unemployment rate is calculated each month by the U.S. Bureau of Labor Statistics. The survey consists of 50,000 households in about 2,000 counties and cities in all 50 states. Stratified. Because you are dividing into subgroups prior to sampling. 2. A researcher for Kraft Foods selects five states randomly, and then selects 10 supermarkets chains within each state to call for a phone survey as test markets for a new cookie. Cluster. You are dividing into groups or cluster then taking a random sample. 3. A new product researcher would like to investigate the use of virtual teams. After conducting an interview with a manager, she asks for the names of other managers that use virtual teams. Snowball. You are using a small pool of subjects and generating more from them. 4. A news reporter asks people on the street their opinion about the president’s new bill. Convenience. There are some members of the population that have no chance of being selected and you are using readily available subjects. 5. Jamie select Denver, Colorado; Chicago, Illinois; and San Diego, California as test markets for a potato chip line base on her experience with these markets. Judgment. Because Jamie has used his or her own judgment to select the appropriate sample. 6. A researcher instructs field interviewers to interview customers of different cell phone companies in a nearby shopping mall so that they each interview 10 AT&T, 8 T Mobile, 6 Verizon, and 4 owners of other cell phone providers. Quota. Because there is a set requirement of the sampling pool. 7. The Consumer Price Index represents a sampling of 90,000 items from 364 categories, chosen from 20,000 retail stores in 85 geographically distributed areas that are chosen to be as similar as possible. Stratified. Because you are dividing into subgroups prior to sampling. 8. A finance professor wants to know how many MBA students would be willing to take a course in international finance this summer. She surveys students in the class she is currently teaching. Cluster because she is dividing all MBA students into a group and sampling her class. It could also be seen as Convenience because she is sampling a group that is on hand and there is a set that doesn’t have a chance to be selected (anyone not in her class).

The Biggest Myth About Toulmin Model Essay Topics Exposed

The Biggest Myth About Toulmin Model Essay Topics Exposed Choosing Good Toulmin Model Essay Topics A Toulmin warrant is likewise an assertion. however, it is of such a sort that does not require additional proving (in this sense it's a presupposition). Needless to say, this argument is only of ideal nature, so it's impossible to adhere to it in an ideal sense. In fact, this kind of argument is targeted at finding common ground. Toulmin arguments consider the intricate nature of the majority of situations. What the In-Crowd Won't Tell You About Toulmin Model Essay Topics A youngster's beauty pageant is composed of contestants that range from ages as young as three all the way up to eighteen decades old. The writer's major claim is that the wearing of school uniforms shouldn't be enforced. With America being known as the melting pot of the Earth, our society has many people with family on the opposite side of the Earth. Usually, this style is beneficial for stubborn audienc es. If writers use qualifiers which are too broad, including always or never, their claims can be quite tough to support. You also need to think about whether a warrant is in fact an unproven claim. You should back up your viewpoint with well-researched facts and data also. Just about any certain topic can lend itself to be stated among the five kinds of claims. Therefore, there's a need to prevent the rising of the temperatures before it's too late. On the other hand, the little increase in global warmth was shown to be caused more by a rise in carbon dioxide in the atmosphere aside from the naturally occurring natural fluctuations. When it can be argued that the growth in temperature is extremely gradual, it is necessary to think about the upcoming generation. Some can argue that the quantity of carbon dioxide is so small to cause the growth in temperature. There's, obviously, a limit on the variety of pages even our finest writers can produce with a pressing deadline, but usually, we can satisfy all the clients seeking urgent assistance. You may also secure many discounts on our site which will help you to save some more money for future orders or anything you want to spend them on. Our customer support will gladly tell you whether there are any special offers at the present time, along with make sure you are getting the very best service our business can deliver. An excellent start is a guarantee of succeeding. Ideas, Formulas and Shortcuts for Toulmin Model Essay Topics Getting the opportunity to go to school when playing sports is such a fantastic thing for an individual's future. Questions are a standard means of getting interest, and evocative language or a strong statistic Don't assume your audience is already acquainted with your topic. The difficulty could be in trying not to lose your primary idea among the huge amount of information. Naturally, you may choose any other topic. Understanding Toulmin Model Essay Topics At some stage, you're likely to be requested to compose an argumentative essay. An argumentative essay requires you to choose a topic and have a position on it. A very good argumentative essay is going to be based on established or new research in place of only on your ideas and feelings. Among the many types of essay, there's a definition essay that could appear to be among the most simple assignments. When writing an argumentative essay, you might choose one of these methods and this is the way you know which is the best one for you. If you still doubt whether you are able to deal with this kind of assignment for a definition essay alone, we're delighted to inform you that there's a fantastic solution! If you're looking for Toulmin essay idea, here are a few great topics you can test out. Quite frequently, the very best topic is one which you truly care about, but you also will need to get well prepared to research it. The Bizarre Secret of Toulmin Model Essay Topics It is recommended to look for the one which has a superior reputation and offers high-quality papers at economical rates. The best option is to make an outline. Additionally, a customer may ask the writer to submit part of the job for review and, if needed, ask her or him to make corrections. So, the very best start would be to interpret this kind of assignment for a definition essay so as to define and unders tand its features that have to be preserved. The Importance of Toulmin Model Essay Topics Therefore, there might be other aspects which influence the specific benefits in school. The prevalence of the net has caused an increase in plagiarism amongst students. A student that doesn't have accessibility to a computer at home is disadvantaged when homework needs to be banned because of these reasons that have. Write about a present issue like the effects of tablet computers rather than textbooks, or methods to prevent school bullying. The Argument About Toulmin Model Essay Topics You will need to develop a fantastic argument, which encompasses not just your principal point, but also all the pieces which make this up. As you answer these questions, you will have the ability to identify what kind of an argument you're making. This thought of disarming those who can earn a positive distinction is most likely one of the biggest disgraces as soon as it comes to gun control (Warrant). It is likewise very important to research natural variations. If you wish to compose a productive argument you must pick the point you wish to make and the audience you wish to make it to. In fact, Rogerian rhetoric can be regarded as a peculiar variant of the democratic debate. Your parents are somewhat more likely to reply positively to the second argument for the reason that it demonstrates that you've done something to deserve the higher allowance.

Mobile Technology And Its Effect On Our Society - 939 Words

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