Magnetic Nanoparticles For Cancer

Running head: MAGNETIC NANOPARTICLES FOR CANCER 1

Magnetic Nanoparticles for Cancer

Pulkit Bharat Patel

University of South Florida

MAGNETIC NANOPARTICLES FOR CANCER 2

Abstract

Nanoparticles nowadays play a significant role in the site-specific drug delivery system.

Nanoparticles have been well applied in the field of Nano medicine where the drug is delivered

to the target cell using external magnetic field. Magnetic nanoparticles related drug delivery

leads more attention than other therapy. Cancer has been one of the dangerous diseases in the

plane. Various types of cancer such as brain cancer have been difficult to treat because of the

manifestation of blood-brain hurdle and skull that prevents delivery of a drug to the brain.

However, Magnetic nanoparticles have portrayed great effort towards the treatment of the

various types of cancer compared to the traditional methods of treating cancer. The research will

focus on various advancements that have been made based on MNPs which will include

magnetic hyperthermia, the controlled delivery of the drug and specific targeting using magnetic

fields. The research will focus on the brain cancer. In such a way, the literature review will

evaluate the way in which MNPs provide drug delivery for the brain cancer.

MAGNETIC NANOPARTICLES FOR CANCER 3

Contents

Introduction ..................................................................................................................................... 5

Literature Review............................................................................................................................ 5

Thermotherapy ................................................................................................................................ 7

Hyperthermia .................................................................................................................................. 8

Techniques for synthesis of MNPs ................................................................................................. 9

Problem statement ......................................................................................................................... 12

Brief Description and goals of the study ....................................................................................... 15

Discussion ..................................................................................................................................... 16

Methodology ................................................................................................................................. 17

Research Setting ........................................................................................................................ 18

Population and Sample .............................................................................................................. 18

Sampling criteria ....................................................................................................................... 18

Sampling technique ................................................................................................................... 18

Ethical consideration ................................................................................................................. 19

Data collection........................................................................................................................... 19

Pilot Study ................................................................................................................................. 20

Plan for Data Analysis............................................................................................................... 20

Estimated Costs ......................................................................................................................... 20

Research proposal budget ............................................................................................................. 21

MAGNETIC NANOPARTICLES FOR CANCER 4

References ..................................................................................................................................... 22

MAGNETIC NANOPARTICLES FOR CANCER 5

Introduction

Magnetic nanoparticles (MNPs) have for decades shown a significant potential in

biomedicine. Maybe the best-known presentation of these particles is a different agent of

magnetic character imaging (Veiseh et al., 2010). However, their presentations are spread

widely. The magnetic nano-particles are always used as movers for organized delivery of drugs.

Triggered drug release and magnetic targeting escalate the drug dose at a targeted site. The other

use of magnetic nanoparticles (MNPs) is treatment of tumors and other contagions by

hyperthermia induced by controlled magnetic field. Therefore, the large number of presentations

call for the question: will it be possible to join many applications to make a single non-in vase,

broad therapy for tumors? The therapy will comprise of imaging, targeting, and treatment by the

use of the same magnetic nanoparticles for all stages of the therapeutic procedure. Targeting

results into the precise gathering of particles at the area that was affected after which an imaging

strategy will verify if the particles are delivered to the area that was targeted and the quantities

that will be present. If the particles are put in place, treatment can begin so that it is only the

targeted area that is affected. Additionally, the adverse effects in the affected area are reduced to

the minimum. Active magnetic resonance imaging makes use of different imaging systems to

identify abrupt cell production in a soft tissue. Magnetic resonance imaging (MRI) principle

makes the main difference between surrounding the tissues and magnetic slackening (Veiseh,

Gunn & Zhang, 2010). Chemotherapy is one of the common methods that are used to treat

cancer. It is practical that when many distinct antitumor are introduced, the entire body gets

exposed to these therapeutic particles.

Literature Review

MAGNETIC NANOPARTICLES FOR CANCER 6

Parv, Sahoo & Misra (2012) argue that the interest of applying nanoparticles in delivering

drugs has grown tremendously for the last ten years. This has been attributed to the effectiveness

of MNP in delivering drug and its unique properties. MNP offer dual diagnostic tool as well as a

targetable drug carrier for cancer therapy. What is common about the nanoparticle based

therapies of cancer is the requirement of the particular NPS to achieve the right therapeutic effect

(Parv, Sahoo & Misra 2012). However, the therapeutic or diagnostic technique needs a different

physical or chemical property of the involved particles that depends on particular functions

played by the nanoparticles in the therapy such as healing agent, receptacle, and magnetic

moment carrier (Veiseh, Gunn & Zhang, 2010). At times, the particular function is normally

activated with the use of external agent, radiation, and magnetic fields, light which interacts wth

nanoparticles. As such, the NPS requirements as biomedical agents need numerous materials,

research fields and synthesis strategies.

Cheng (2013) states that MNPs play a significant role in imaging brain cancer. They

provide a sensitive contrast enhancement due to their inherent ferromagnetic qualities. In the

brain tumors, the accumulation of MNPs occurs as a hypointensity on the T2 weighed imaging

that includes the gradient echo imaging. The MNPs is modified in such a way that it causes

effects only to the target cancer cell in the brain through medical resonance imaging. Using

MNPs as a carrier for MRI provide a more sensitive imaging on the brain cancer cells. This has

been one of the standard methods to visualize tumors of the brain. One of the most significant

subclass of MNPs that is used in imaging is the Ultra small superparamagnetic iron oxide

nanoparticles (USPIONPs) (Alexio et al, 2006) they have a greater half –life compared to the to

the standard MNPs and can be used for longer time through the Medical Resonance Imaging (Di

Corato, 2011). The current study indicates that USPIONPs is used to detect increased blow flow

MAGNETIC NANOPARTICLES FOR CANCER 7

in the regions with brain tumor. Furthermore, USPIONPs help to monitor pseudo progression in

brain tumors following the therapies such as chemotherapy and radiotherapy.

According to Cheng (2013), the nanoparticles provide the likelihood of drugs to be directed

systematically but focused to a particular target cell tissue in the body while at the same time

remaining localized, through the application of means of the magnetic field. Despite the fact that

the use of the magnetic particles in the delivery of drug was proposed in 1970, the magnetic

delivery field has received the necessary attention, recently. The therapeutic agent usually

condensed within the magnetic nanoparticle and polymer of the nanocomposite mixture. They

may be influenced by the reduced applied magnetic field values, the ideal nanoocoplexes idea

properties that are used should have high magnetization values at the temperature if operation.

Thermotherapy

Veiseh, Gunn & Zhang (2012) argue that as a result of the negative side effect and

toxicities that develop when the brain is subjected to hyperthermia for a long period, localized

treatment is important when dealing with patient with brain tumor therapy. The implantation of

MNPs directly to tumors in the brain help in bypassing blood brain barrier which allow

maximum hyperthermia effects to the target tissue. Following the injection of MNPs into the

tumors, the Magnetic nanoparticles (MNPs) get depicted to alternative magnetic fields (AMF)

where warmth is then produced through the Brownian Neel relation process (Veiseh, Gunn,

Zhang 2010). Thermotherapy refers to the application of the alternating magnetic field. Once

magnetic field is applied onto the target areas, hypothermic treatment rely solely on various

factors such as the strength of AM, the time when the field is administered to the tumor as well

as the concentration and size of the MNPs.

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Targeting the specific cells is essential since the prolonged exposure to the health cells can lead

to side effects in the body (Veiseh et al., 2010). In order to minimize toxicities that may occur as

result of hyper thermic treatment, MNPs is administered in certain duration of time to the targets

cells which enable it to heat up leading to death of cancer cells. The hyperthermia of temperature

that ranges between 42oC and 490 C in patients with brain tumors is safe and very few negative

effects are experienced during the entire process.

Thermotherapy initiates the death of malignant cells. The internal temperatures of MNP

increase when it exposed to alternating magnetic field (Veiseh et al., 2010). Consequently, the

heat is transmitted to the neighboring abnormal cells located on the surface of nanoparticles

which further lead to death of the tumor cells. In the case of chemotherapy, only the targeted

region is exposed to high temperature which results to necrosis. However, there are some

limitations that occur as when MNPs is used when diagnosing the brain tumor. For instance, high

levels of MNP are required to generate hyperthermia that inhibit the use of MRI and ensure that

MNPs are administered in the right way to the target tissues.

For cancer therapy and diagnostics, there exist several techniques that are based on

various nanoparticles types the Nano-technological advances are claimed to be at the bottom of

the coming paradigm shift in cancer research (Parveen, Misra & Sahoo 2012). Therapy and

diagnosis is done through improvements of the malignant cells direct visualization, and the

targeting done at the molecular level delivers huge amounts to the chemotherapeutic agents to

the required cells. Such techniques allow faster and sensitive detection of the malignant cells

when they are the early stages.

Hyperthermia

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Veiseh, Gunn & Zhang (2010) argue that treatment of different types of cancer using

Hypothermia has been well studied in the past. Increase in temperature above 40oC in the

targeted areas can lead to death of the cancer cell. Additionally, some studies have indicated that

moderate hyperthermia at a temperature of about 45oC is adequate to initiate the death of cancels

in the brain (Veiseh, Gunn & Zhang 2012). Nonetheless, regional hyperthermia can lead to

elevation of the blood flow which subsequently assists in the delivery of other treatments such as

chemotherapy that might lead to synergistic antitumor effect. Even though hyperthermia can be

used in treatment of cancer, brain tumors are being difficult due to presence of skull which

prevents the delivery of drugs to the system. Heat applied to the brain sometime fail to reach the

target cells because of the brain blood barrier and skull that surround the brain. When

temperature elevation in the brain occurs for a prolonged period of time, it can cause side effects

and toxicities to the patient. MNPs can be administered intratumorally before treatments with

magnetic fields, this ensure that the abnormal cells in the brain are reached. Chemotherapy

administers high levels of hyperthermia effect to the tumors which help to reduce the heating that

surround the brain.

Techniques for synthesis of MNPs

Even though materials that contain nickel and cobalt have been studied, MNPs that are

made up of iron oxide core are the most studied due to their effectiveness in reducing toxicity in

the body (Veiseh, 2009). The MNPs are usually coated with material for good compatibility. The

coating shell structure helps to stabilize the MNPs in the physiological fluids.

The magnetic properties of cobalt and iron are utilized in these instances because of their

properties in magnetic MNPs (Veiseh, Gunn & Zhang, 2010). In most cases, such particles can

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possess the magnetic cores with a polymer of non-metals (such as silica or gold) and metals or

the external coating. Also, the particles can be Nano composite mixtures made up of the MNPs

that are condensed within the porous polymer. Presence of different metal or nonmetal coating or

polymers provides the opportunity of anchoring different DNA or therapeutic drugs for the

targeted gene delivery (Chen, Zhang, Chen, Zhang & Zhang, 2010). A different approach is

found in the condensing the cytotoxic drug besides the magnetic Nano spheres in the matrix

polymer.

After the encumbering of the therapeutic moiety to nanoparticles sited in vivo, the

magnetic Nano centers are normally focused at site of the target with the use of the unusual

world magnets of great field (Veiseh, Gunn, & Zhang, 2010). High gradient presence focused on

a particular site on forces of the body and captured particles at the tissue targeted. Even though

such may be a good strategy of the targets near to the exterior of the body, the effect disappears

for the applications within a person’s body, as the strength part of the magnetic field decreases

steadily with distant and inner sites becoming hard to aim (Chen, et al., 2010). Several groups

want to circumvent the issue by inserting the electromagnets in the body close to the target site.

The particles of magnet do not have to retain any magnetization remnant once there is the

removal of the magnetizing field. Such avoids magnetic nanoparticles aggregation because of

bipolar interactions between the magnetizations and facilitates their body excretion.

There are various production routes of MNP. For instance, a simple method involves the

precipitation of iron salts. Nonetheless, precipitation using the reverse micro emulsions has also

been successful conducted. Even though the technique does not produce MNPs of smaller size,

the micro emulsions are always associated with low yields. Currently, the decomposition of

organometallic compounds has attracted significant attention from the scientists (Cheng, 2010).

MAGNETIC NANOPARTICLES FOR CANCER 11

The technique well monitors the final size of the particle, crystal structure and shape compared to

other method. However, the reaction takes place in the organic solvent which contains the

hydrophobic stabilizers (Veiseh, Gunn, Zhang 2010). The stabilizers provide the additional

surface modifications which allow nanoparticles to have greater aqueous stability. Surface and

size properties of Magnetic nanoparticles play an essential part on the behavior of nanoparticle

especially in colloidal stability, pharmacokinetic functions as well as ease of coupling with

ligands. Hence, paying attention to both surface character and size is important towards the

development of MNPs in in vivo platform. In cancer therapy, MNPs have been studied more

compared to medical resonance imaging. The increased susceptibility of MNP provide the strong

enhancement in the transverse T

) regions where nanoparticles are localized. Strong relativity

is experienced in the T2 transverse. Not surprisingly, the MNPs method has been used

successfully in MRI investigations.

Parv Sahoo & Misra (2012) claimed that the magnetic nanoparticles may be of significant

for therapy and analysis of brain tumors. Targeting nanoparticles across the BBB (blood brain

barrier) if through improved retention and permeation effect. However, permeation and mention

effect may be limited by the tumor environment (such as fibrosis, hypovascularity, or necrosis),

even during the time when the pathogenic processes hinder the function or integrity of the BBB.

MPS of the iron oxide was developed by encapsulating then within polymers (Gubin (ed), 2009).

The epirubicin, anticancer agent restrained on MNPs surface. Such novel delivery system of the

magnetic drug was directed to the brain by using focused ultrasound and magnetic pointing as a

delivery system that is synergistic (Chen et al., 2010). Both the externally applied magnetic field

and ultrasound increase concentration of MNP. The results reeved that control aims revealed no

accumulation of MNP in tumor region even after six hours administration of MNP. However, by

MAGNETIC NANOPARTICLES FOR CANCER 12

applying exterior magnet, about 14-fold than epirubicin therapeutical ranging per tissue gram

was absorbed by the cancer cells. Fluorescence microscopy adds confocal staining and prussian

blue confirming epirubicin-Magnetic nanoparticle presence at the tumor than inside of

contralateral.

Generally, using MNs as a drug is understood as the selective targeting and

biocompatibility at the desired tissue or cell udder exterior magnetic field guidance. Advances in

technology and development of MNs as treatments to hypoxic areas were enhanced in the last

era and caused improvement of different electromagnetic Nano designs like metallic, polymeric,

nonmetallic, and liposomes (Chen et al., 2010). Such important drug systems have increased the

capacity of delivering drugs that the traditional therapy has shown not to be effective. The

technology is there to minimize invasive procedures and reduce the healthy tissues side effects

that are the major concerns of conventional cancer brain therapy. Magnetic treatment is

developing and synthesis of effective magnetic treatment, integration and delivery of different

functioning particles are examined to allow its full use in clinics and healthcare facilities.

Problem statement

Cancer is the greatest proliferation of cells. To date, it is the most life-intimidating

challenges globally. Customary curative choices for malignant tumors include chemotherapy,

radiotherapy, and surgery. Unluckily, at times surgical eradication is not possible because of the

unfavorable tumor stage, inadequate organ functional backup, location and high functioning risk

to the patient. Radiotherapy and chemotherapy have the disadvantage of affecting the healthy

tissues and are costly to the society. Hyperthermia comprises of locally heating the tumor tissue

and is slightly cheap (Chen et al., 2010). Above all, it has few side effects to the patients. Cancer

MAGNETIC NANOPARTICLES FOR CANCER 13

cells depend on a small (narrow) temperature range and therefore can be destroyed by heat over

time. Besides, hyperthermia improves the effect of chemotherapy and radiotherapy. Based on

magnetic nanoparticles hyperthermia comprises locally heating tissue whereby the magnetic

nanoparticles use exterior radio in various magnetic fields. Magnetic fields are usually used in

biomedical engineering for they can enter biological tissues. A current that flows through a coil

can generate a magnetic field that is time-varying. This magnetic field can interact with the

magnetic material and result in heating of magnetic material due to the different kinds of loss

processes. Particular mechanisms that lead to the warming of the magnetic field cannot be

captured entirely and hamper the applicability of magnetic nanoparticles based on hyperthermia.

Usually, heating of the tissues with an elevation beginning from 5oC prompts a sequence of

biological processes resulting in the degradation of tumor cells. The key effect begins with

thermal de-activation of mitochondrial vigor alteration in the cell. The next stage degrades and

dissociates the cellular membranes. The delayed thermal effects look as pathologic reactions to

tissue and cell injury.

In spinal metastatic tumor illness, the vertebral column is invaded and debilitated by

diseased tissue that leads to liberal compression of the spinal cord and failure of the vertebral

body. In turn, this might lead to a serious deficit in the neurological function. Currently, some

methods agree to either treat or stabilize the spinal column. These approaches include the

vertebral body increase by injection of ‘cement' that goes by the name "PMMA,

polymethylmethacrylate." Another method is vertebroplasty which entails the injection of

PMMA using a powerful device (Chen et al., 2010). There is also another method that is known

as kyphoplasty that entails creating of a cavity in the vertebral column using a balloon before

getting to fill it with PMMA at comparatively low pressure. All these methods readily stabilize

MAGNETIC NANOPARTICLES FOR CANCER 14

the spine although they do not stop the progression of the tumor. The current spinal metastatic

illness treatments like the most common and standard radiofrequency ablation, laser-induced

thermotherapy strategies and neurosurgery are done before injection of the cement hence they

can only be done once. Surgical actions are possible for 10 to 20% of the patients, however

because of the recurrent progression of the spinal metastases, the surgery requires to be repeated

which is unwanted and expensive for the patient. No modality integrates both treatments of

spinal metastases and stabilization of the spinal column. Because of the progression of the spinal

metastases, treatment needs to be done repetitively with little additional aggressive

manipulations. This project proposes the understanding and development of therapy that makes

use of nanoparticles in the treatment of tumors and administration of drugs. Therefore, the

cement that is loaded with magnetic nanoparticles might be administered clinically in a less

invasive manner as it is done in kyphoplasty or even vertebroplasty. Magnetic nanoparticles may

then be triggered using an externally made magnetic field to heat the bone cement thereby

enclosing the biological tissue. Magnetic nanoparticles can be magnetic resonance scanner

compatible to make it possible for accomplishing radiology with no artifacts. Heating of the

magnetic nanoparticles happens because of the magnetization processes between and within

them. Development of therapy device is technologically challenging because the needed

magnetic fields are high in both frequency and amplitude (Chen et al., 2010). The current

magnetic nanoparticle centered hyperthermia requires magnetic induction fields that range from

0.05T to 0.1T and magnetic field frequencies that range from 100-260 kHz. To attain these high

amplitudes and frequencies is hard due to the high currents and needs the inflow of the

excitation. It is only possible by cooling the excitation coil internally by using a resonance circuit

capacitor.

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Brief Description and goals of the study

The proposed project aims to guide the nanoparticles into cells that are targeted by using

magnetic fields (Di Corato et al., 2011). When the nanoparticles get to the cells, they get to be

forced into the cancerous tissues by ultrasound through the sonoporation. Preferably, the study

shall focus on how to optimize the uptake of nanoparticles and give an insight into why the

methods that entail the use of nanoparticles.

After carrying out numerous literature studies on imaging, targeting, and treatment, it was

evident that there are many presentations of MNPs that have many possibilities of jointing to

come up with one therapy. As the main requirements for a perfect therapy, general applicability

and non-invasiveness will be taken to be essential. So, as the focus and preferred choice of this

study, ‘Enhanced Permeability and Retention' outcome is seen as the main targeting method,

hyperthermia as the actual treatment and CT(Computer tomography) is for visualization (Gubin,

2009). It is evident that the named choices are universal and non-invasive. Regarding the issue of

targeting, the Improved Permeability and Retaining effect was selected to be the method used

because of its ease of use and non-specifity. Solid tumors are susceptible to this effect with no

extra therapeutic actions. Various methods of targeting such as ligands and the utilization of

tumor precise-receptors are not applicable, and by that, they will not be accepted. Similarly,

invasive strategies like direct inoculation of surgical replacement of a magnet in the tumor and

therapeutic agents will be discarded.

Hyperthermia was selected as the promising option of treatment because of its

universality (Di Corato et al., 2011). On top of its universality, the method has got other

advantages such as the only harm of the particles is the heat that is generated after they are

MAGNETIC NANOPARTICLES FOR CANCER 16

stimulated by alternating magnetic field. The use of controlled magnetic field further

supplements the targeting of the treatment which in return reduces the hostile effects.

Because hyperthermia requires a huge concentration of magnetic nanoparticles, CT (Computer

Tomography) was seen as the best choice over MR (Magnetic Resonance) imaging to picture

these huge quantities. Reasoning that attributed to this is that at high concentrations, magnetic

resonance imaging cannot determine the actual quantity and location of the MNPs while

Computer tomography excels at relatively high concentrations (Gubin, 2009). Photoacoustic

imaging is another promising new strategy although it has not been fully developed to be a

valuable option.

Discussion

Veiseh, Gunn & Zhang (2010) state that the goals of nanoparticle entrapment of medicine

are either uptake or delivery to targeted cells and the reduction of toxicity of free drugs to organs

that were not targeted (Alexiou et al 2006). These situations will lead to a rise in the therapeutic

index gap in doses that lead to tumor cell efficacy. Many of the compounds are polymers that are

biodegradable that lead to drug release after they have degraded. One of the challenges of using

nanoparticles in drug delivery is entrapment in mononuclear phagocytic systems. Conversely,

liver targeting of nanoparticles might be boosted when handling liver diseases such as hepatitis

and tumor metastasis. Modification of the surface with polyethylene glycol will lead to

prolonged availability in the circulation by constraining phagocytosis using the phagocytic

system. On top of altering the displacement of PEG modification, the coating of the NP might be

essential to prevent accumulation. Many coatings might be used to prevent agglomeration and to

maintain the particles in colloidal suspension.

MAGNETIC NANOPARTICLES FOR CANCER 17

Besides, physical methods like light and heating can be used to provoke the therapeutic effect or

local release of drugs (Alexiou et al 2006). Therefore, thermosensitive nanoparticles can be

employed for the release of drugs after a given localization. Additionally, releasing of

photosensitizers by light which is known as photodynamic therapy can induce cytotoxicity as

shown by the nanoparticles that contain indocyanine green and zinc phthalocyanine.

The big challenge is the drug delivery to a target body place with minimum side effects to

non-targeted organs (Di Corato et al., 2011). This is the outstanding challenge in the treatment of

cancer because the tumor might at times be localized as different metastases in different organs.

Therefore, the non-restricted toxicity of the chemotherapeutics hinders the full use of the

potential of the therapeutic. Nanoparticles have precise particles/tools that enhance these

strategies. Their small size gives room for the permeation of the walls of the cell membranes,

lysosome outflow after endocytosis and stabilization and binding.

The strategy of magnetic hyperthermia is built on the principle that the local tissue’s

temperature is increased to about 41oC to around 43oC by using the fluctuating magnetic field

for some time. The energy that is obtained from the application of magnetic field is combined in

the nanoparticles (Alexiou et al., 2006). Besides, it is this that gets converted to thermal energy

with the help of a quantified rate of absorption. Nanoparticles get attached to the affected tissue

by active targeting and passive targeting. The active targeting is attained by the use of the

application of the magnetic field because of the functional specificity of various agents such as

folic acid. Passive targeting refers to heightened retaining of nanoparticles in the tumor cells. It

also includes increasing permeability.

Methodology

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Research Setting

The study will be carried out in the Sharide Sai Baba Cancer Hospital and Research

Center. The hospital can hold many cancer patients. It can handle all types of cancer ranging

from the brain to breast cancer. Besides, it has a high turnout of cancer patients. Therefore, this

will make it easy for researchers to get subjects.

Population and Sample

The population of this study will comprise of breast, brain and metastatic spinal tumor

illness patients from south Karnataka, Kerela, and Goa who attend Sharide Sai Baba hospital and

research center for treatment and medication (Gubin, 2009). Sample size will be estimated using

the concept that observation should be 5-10 times the variables in the regression model. A

representative sample of 300 patients who receive cancer treatment during March 2018 to 2021

will be surveyed and interviewed. Demographic proforma, disease and treatment details for all

subjects will be collected.

Sampling criteria

The patients who have been diagnosed with cancer and are receiving treatment are the

ones that will fulfill the criteria for inclusion and will be considered for the study (Veiseh, Gunn

& Zhang, 2010). The ward admission register, as well as the statistics of records that are

maintained by the medical records unit, will be relied on for finding suitable subjects for the

research.

Sampling technique

MAGNETIC NANOPARTICLES FOR CANCER 19

The study will adopt a suitable purposive sampling strategy for recruiting participants for

the study (Gubin, 2009).

Ethical consideration

The researchers should receive permission from the medical superintendent of the

hospital. There will be a written informed consent from the participants (Chen et al., 2010) Also,

the study shall have ethical clearance from the ethics committee of the institution and informed

consent by the subjects will be availed before commencing the study.

Data collection

The study will be observational, perspective and follow up. Patient interview, structured

questionnaire, and review of the patients' record shall be adapted to collect data that is related to

the quality of life advantages of nanoparticles and background information of the patients.

Information about diagnostic tests, demographics, and treatment details, as well as other clinical

features, will be obtained from the medical records, the histopathology reports, laboratory reports

and patient discharge summaries of every patient (Di Corato et al., 2011). The outpatient

department shall be consulted to provide information that will aid in measuring the efficiency of

nanoparticles among other features. There shall be personal visits to the wards and outpatient

facilities where the cancer patients are admitted, and the researcher shall personally interview the

subjects. After giving an explanation and obtaining the patients' consent, the subjects will be

included in the research. Questionnaires that contain cancer-specific modules shall be

administered. Quality of life shall be measured on those who have undergone a minimum of 3

courses of chemotherapy. The difficulty of understanding the questionnaire shall be clarified as

assistance will be offered to the subjects who will need it. Repeated follow-ups on monitoring of

MAGNETIC NANOPARTICLES FOR CANCER 20

ADR, morbidity, and QOL will be done and documented during the courses of therapy.

Information pertaining costs shall be obtained by carrying out interviews with the patients and

their relatives. The clinical outcome shall be summarized by checking the case records and

history of the patients in 1-2 years of the study duration. Cost evaluation shall be carried out

following the expense of consultation, surgery, diagnostic investigations, pharmacological

management, radiotherapy charges and another cost for cancer treatment right from diagnosis to

end of preliminary treatment.

Pilot Study

A pilot study shall be carried out by giving free nanoparticle services to 30 patients

during January 2018 in Shirdi Sai Baba cancer hospital to discover feasibility of the project. The

study shall begin after receiving a clearance form from the institutional ethics board. The data

obtained shall be analyzed to determine whether the study project is feasible or not.

Plan for Data Analysis

Data shall be analyzed by the objectives by the use of inferential and descriptive

statistics. The applicability, side effects and treatment costs shall be calculated for different

cancer treatment arms.

Estimated Costs

The cost of the research is expected to be $177,700 per year, approximately $710,000

over a four year period. Part of the money shall be availed by the school. The remaining shall

come from research grants. Grants shall subsidize the expense of using the tools (Alexiou et al

2006).

MAGNETIC NANOPARTICLES FOR CANCER 21

Research proposal budget

Grant request

University share

Total personnel

65,000

21,000

Fringe Benefits

15,000

5,200

Equipment

20,000

Travel

10,000

Supplies and materials

19,500

10,000

Consultants

12,500

Subcontract

8,000

Printing

1,500

141,500

36,200

MAGNETIC NANOPARTICLES FOR CANCER 22

References

Alexiou, C., Schmid, R. J., Jurgons, R., Kremer, M., Wanner, G., Bergemann, C., ... & Parak, F.

G. (2006). Targeting cancer cells: magnetic nanoparticles as drug carriers. European

biophysics journal, 35(5), 446-450.

Di Corato, R., Bigall, N. C., Ragusa, A., Dorfs, D., Genovese, A., Marotta, R., ... & Pellegrino,

T. (2011). Multifunctional nanobeads based on quantum dots and magnetic nanoparticles:

synthesis and cancer cell targeting and sorting. ACS nano, 5(2), 1109-1121.

Chen, F. H., Zhang, L. M., Chen, Q. T., Zha, Y., & Zhang, Z. J. (2010). Synthesis of a novel

magnetic drug delivery system composed of doxorubicin-conjugated Fe 3 O 4

nanoparticle cores and a PEG-functionalized porous silica shell. Chemical

Communications, 46(45), 8633-8635.

Gubin SP (ed) (2009). Magnetic nanoparticles. Wiley-VCH Verlag GmbH and

Co,KGaAParveen, S., Misra, R., & Sahoo, S. K. (2012). Nanoparticles: a boon to

drug delivery, therapeutics, diagnostics and imaging. Nanomedicine:

Nanotechnology, Biology and Medicine, 8(2), 147-166.

Veiseh, O., Gunn, J. W., & Zhang, M. (2010). Design and fabrication of magnetic nanoparticles

for targeted drug delivery and imaging. Advanced drug delivery reviews, 62(3),

284-304.

MAGNETIC NANOPARTICLES FOR CANCER 23

Veiseh, O. (2009). Development of multifunctional nanoparticles for brain tumor diagnosis and

therapy. University of Washington.

Parveen S, Misra R, Sahoo SK (2012). Nanoparticles: a boon to drug delivery, therapeutics,

diagnostics and imaging. Nanomedicine-Uk.;8:147–66. doi:

10.1016/j.nano.2011.05.016

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