Magnetic and Hypoxic Biosensor As a Vehicle For

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Idris et al. World Journal of Pharmacy and Pharmaceutical Sciences SJIF Impact Factor 7.632 Volume 8, Issue 12, 316-320 Review Article ISSN 2278 – 4357

MAGNETIC AND HYPOXIC BIOSENSOR AS A VEHICLE FOR

CHEMOTHERAPEUTICAL DRUGS

Mithaiwala Idris A.*1, Suthar Hetal S.1, Ojha Sunil1 and Agrawal Amit2

1B Pharmacy College Rampura, Godhra, Gujarat. 2Aditya College of Pharmacy, Satna, M.P.

Article Received on ABSTRACT 24 Sep. 2019, Cancer is deadly disease which is caused due to uncontrolled growth of Revised on 14 Oct. 2019, Accepted on 04 Nov. 2019, the cells and forms an extra mass of tissue which is known as

DOI: 10.20959/wjpps201912-15051 tumor. One of the biggest challenges in cancer therapy is to deliver drug to the tumors without exposing the healthy tissue to their toxic *Corresponding Author effects. Using gamma radiation in chemotherapy to destroy the tumors, Mithaiwala Idris A. the healthy tissue also with the tumors. Oxygen-depleted hypoxic B Pharmacy College Rampura, Godhra, Gujarat. regions in the tumor are generally resistant to therapies. gets destroyed which is the big disadvantage. Yet while the nanocarriers prove to deliver drug to the specialized tumor cell they remain limited as they rely on the systemic

circulation. Omitting all these disadvantages specially featured bacteria provide a future vehicle to drug to the tumors. Magnetococcus marinus which has mainly two properties from which one is, it gets attracted to the magnetic field and the other it navigates to the low oxygen levels, so these bacteria can be a perfect vehicle for delivering Chemotherapeutical drugs to the tumors..

KEYWORDS: Xenograph, chemotherapeutics, nanocarriers, tumor.

INTRODUCTION Cancer is one of the major life threatening diseases in the world. The available anticancer drugs have distinct mechanisms of action which shows varying effects on different types of normal and cancer cells. Chemotherapeutical drugs and radiation destroy the cancerous cell but with that it also affect the healthy cells and has mainly side effects like heart disorder, loss of appetite, hair loss, nausea and vomiting, neural disorder, and many more.

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To overcome chemotherapy the scientist designed nanocarriers. These are small colloidal particles being used as transparent module which release the drugs at specific targeted cell. It consist of micromoleular material which is an active ingredient which is dissolved, entrapped or attached in the transparent module. Nanocarriers are only uptaken by the cancer cells by the mechanism of specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies.

Nanocarriers do an excellent work in protecting the healthy tissue still the amount of the drug successfully delivered to the tumor remains low. As Oxygen-depleted hypoxic regions in the tumor are generally resistant to therapies and the nanocarriers rely on the systemic circulation to deliver the drug to the tumor, so large percentage of the drug is filtered out of the body even before reaching their targeted destination. Combining the enhanced permeability and retention (EPR) effect of nanocarriers with longer systemic circulation properties achieved following PEGylation has increased the targeting ratio, but still results in a very limited fraction of nanocarriers entering tumors and only 2% of the drug is able to enter the tumors, so to increase the percentage of the drug delivered to the tumor their should be increased propelling forces to penetrate the tumor beyond their diffusion limits is required, thereafter they cannot target the hypoxic zone due to absence of sensory based system.

General mechanism of tumors for adapting to Hypoxia We need oxygen to survive, even the cells in the deepest and the darkest parts of the body cant live without it. But cancer cells have adapted to survive in very low oxygen level and those end up being one of the biggest challenge to deliver drug to tumors.

Tumors rapidly grow, multiply and the network of blood vessel providing oxygen to their cells can’t keep up leaving many cells starved of oxygen This would kill the normal cell but the caner cells have evolved to beat this condition by switching on a protein called hypoxia- induced factor (HIF), which in turn switches on the other molecules inside the cell.

Mitochondria inner workings monitor’s the oxygen level by protein CHCHD4. When oxygen level fall’s below a critical level this protein activates HIF response. In normal cells when this protein is activated it carries out growth of new blood vessels, but when this protein is synthesized in mitochondria of a cancerous cells it gets adapted to work at a very low oxygen level.

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The researchers varied the levels of CHCCHD4 on cancerous cells. When the entire CHCHD4 was blocked it stopped the action of HIF in cells, stopping the cancerous cells growth, importantly preventing the growth of new blood vessels.

When too much CHCHD4 was switched on cancer cells, large amount of HIF was activated, which kick started a sequence of events that allowed cells to survive at a low oxygen level. This proved that more level of CHCHD4 is activated in cancerous cells and hence the cell survive at a very low oxygen level.

Magnetococcus marinus as vehicle for drug Magnetococcus marinus or MCI-1 is a species of Alphaproteobacteria that has the peculiar ability to form a structure called a magnetosome, a membrane-encased, single-magnetic- domain mineral crystal formed by biomineralisation, which allows the cells to orient along the Earth’s geomagnetic field.

They are mainly found in deep waters and rely on two-part navigation system, the first part involves a chain of magnetic nanocrystals which help bacteria to swim in north direction, whenever in the northern hemisphere and part two act like biosensor to navigate to low oxygen levels. MCI-1 are loaded with nanliposomes containing chemotherapeutical drugs and are injected through IV pathway and computer –programmed magnetic field is switched ON and the bacteria are directed towards the targeted tumors. Once the bacteria reaches the target organ the magnetic field is switched OFF, due to the attraction towards the low oxygen level they penetrate inside the deep layers of tumors and deliver the chemotherapeutical drug to destroy the tumor.

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(a) MCI – 1 Bacteria. (b) MCI – 1 Bacteria loaded with nanoliposome.

Experimental Section To inquire the concept magnetically guided live MC-1 cells in HCT116 xenografts, 20 mice were peritumorally injected with ∼5×107 bacteria in 50 µl PBS solution. Two groups were assessed: an experimental group (group I), which was submitted to a 30 min directional magnetic field using a specially made platform and a control group (group II), which was not exposed to magnetic field.

The color superimpositions in Fig 1 show the MC-1 distributions in the xenografts of group I (Fig. 1A) or group II (Fig. 1B) mice.

Fig 1A

Fig 1B www.wjpps.com Vol 8, Issue 12, 2019. 319

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This correspond the result that the number of bacteria under the influence of magnetic field, reached at the site of target more compared to the non magnetic influenced ones.

CONCLUSION These bacteria in the future may provide a perfect carrier for delivering chemotherapeutical drugs and provide a cheap and rapid treatment for cancer, as with the help of bacterial penetration in the hypoxic cancerous region it increases the possibility of, the amount of the drug delivered successfully to the tumor.

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