nanoparticles against cancer cells

1. Mechanistic investigation on the toxicity
of MgO nanoparticles toward cancer cells
By
N. MOHAMED FAIZEE
13-PCH-19
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2. 2

3. Contents
About Nanoparticles
Advantages and disadvantages
Abstract
Introduction
Experimental methods
Result and discussions
Conclusion
References
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4. What is nanoparticles(NPs)
A nanoparticle (or nanopowder or nanocluster or nanocrystal) is a microscopic
particle with at least one dimension less than 100 nm.
It has large surface area to volume ratio. Nanoparticles exhibit a number of
special properties relative to bulk material.
Color – Nanoparticles of yellow gold and gray silicon are red in color Gold
nanoparticles melt at much lower temperatures (~300 °C for 2.5 nm size) than
the gold slabs (1064 °C)
Absorption of solar radiation in photovoltaic cells is much higher in NPs than it
is in thin films of continuous sheets of bulk material - since the particles are
smaller, they absorb greater amount of solar radiation.
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5. Why NPs for treating cancer?
The NPs guided with a magnet and thus can be localized in
a particular part of the body. Thus, it helps to reduce the side effects of cancer
drugs.
The NPs are more easily caught by tumors than by normal tissues.
NPs are very smaller than the blood proteins so that it can easily passes through
the walls of normal and cancerous cells. Which make them interesting drug
carrier.
High concentration drug getting in to cancerous cells makes them more effective
killing agent with less side effects.
In Chemotherapy: When you administer the drug it goes everywhere; it kills
cancer cells, but it also kills healthy cells.
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6. Why MgO NPs
Other metallic NPs have an effect on both tumor cells and normal human
fibroblasts cells, where as the MgO NPs have an effect on only tumor cells.
The zinc oxide and titanium oxide NPs induced high cytotoxicity in normal
fibroblasts, while magnesium oxide NPs exhibited comparatively low
cytotoxicity on these cells even at high concentrations.
The MgO NPs exhibited low cytotoxicity on normal fibroblasts, and used
to overcome drug resistance in cisplatin-resistant leukemia cancer cells.
The biodegradability and nontoxicity of MgO NPs with their relatively
lightweight properties, excellent thermal properties develop a high-performance
cryosurgery.
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7. Properties and Uses of MgO NPs
Magnesium oxide NPs are odorless and non-toxic. It possess high hardness,
high purity and a high melting point. Magnesium oxide NPs appears in a
white powder form.
It is used for the production of silicon steel sheet, high-grade ceramic
material, electronic industry material, adhesive and additive in the chemical
raw material
High-frequency magnetic-rod antenna, magnetic device filler, insulating
material filler and various carriers used in radio industry
As a fire retardant used for chemical fiber and plastics trades
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8. Antimicrobial effects of various NPs
Nanoparticles Antimicrobial mechanism Clinical and industrial
applications
Ag NPs Release of Ag+ ions; disruption of
cell membrane and
electron transport; DNA damage
Dressing for surgical wound
and diabetic foot; coatings for
medical devices.
ZnO NPs Intracellular accumulation of NPs;
cell membrane damage;
H2O2 production; release of Zn2+
ions
Antibacterial creams; lotions
and ointment; surface coating
of medical device.
TiO2 NPs Production of ROS; cell membrane
and wall damage
Antibacterial agent; food
sterilizing agent; air purifiers;
water treatment systems
Au NPs Interaction with cell membranes;
strong electrostatic attraction
Photothermal therapy with
near infrared light, antifungal
agent.
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9. Advantages of NPs
The use of NPs as delivery vehicles for antimicrobial agents and an effective
therapeutics against many pathogenic bacteria.
NPs-based antimicrobial drug delivery is promising in overcoming resistance to
traditional antibiotics developed by many pathogenic bacteria.
NPs protect drugs from degradation in the body before they reach to the target.
NPs enhances the absorption of drugs into the cancerous cells.
It used for the oncologists to assess the timing and distribution of drugs into the
tissue.
NPs prevent drugs from interacting with normal cells, thus avoiding side effects.
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10. Advantages and disadvantages of antimicrobial
NPs over free antimicrobial agents
Antimicrobial NPs :
 Advantage:
• Targeted drug delivery via specific accumulation
• Lowered side effects of chemical antimicrobials
• Extended therapeutic lifetime due to slow elimination
• Controlled drug release
• Broad therapeutic index
• Low cost
 Disadvantage:
• High systemic exposure to locally administrated drugs
• Nanotoxicity (lung, kidney, liver, brain, germ cell, metabolic, etc.)
• Lack of characterization techniques.
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11. Free antimicrobial agents
 Disadvantage
No specific accumulation
High side effects of chemical antimicrobials
High antimicrobial resistance
Short half life due to fast elimination
Poor solubility
High cost
 Advantage
Absence of NPs in the whole body
Absence of nanotoxicity
Well-established characterization techniques
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12. Other NPs to treat Cancer cells
Gold NPs coated with the drug, which is used to target and kill the cancer
cells.
Gold NPs are non toxic
Gold NPs used to detect the cancer cells and effectively destroy the cancer
cells without affecting the normal cells
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13. Abstract
Magnesium oxide NPs (MgO NPs) are increasingly recognized for their
applications in cancer therapy such as nano-cryosurgery and hyperthermia.
The present study investigated the cytotoxic effects of magnesium oxide
nanoparticles (MgO NPs) against normal lung fibroblast cells and different
types of cancerous cells. MgO NPs exhibited a preferential ability to kill
cancerous cells such as HeLa, and AGS cells.
To investigate the mechanism of cell death occurring in cancer cells (AGS
cells) by the analysis of morphological changes.
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14. Introduction
Cancer is one of the leading diseases throughout the world in which a group
of cells display uncontrolled growth, invasion, and sometimes metastasis.
The present treatments in cancer therapy, including surgery, radiation,
photodynamic therapy and conventional chemotherapy, but they can affect
all the cells in the body.
The nanosized particles with their size comparable to that of biological
structures are very smart materials for the manipulation, sensing, and
detection of biological systems.
Currently, inorganic nanoparticles for biomedical applications has received
more attention due to their pronounced applications as potential
antibacterial agents, drug delivery vehicles, and in molecular diagnostics
and cancer therapy.
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15. Experimental method
Preparation of MgO NPs
By
Simple precipitation method
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16. Mg (NO3)2 (0.1 M) + NaOH (0.2 M) + 50 ml Distilled water
Mixtures continuous stirring with 2h
Formation of white precipitate of Mg(OH)2
Obtained Mg(OH)2 precipitate washed with
distilled water
Dried at 100 ºC and Calcined for 400 ºC
Formation of MgO NPs
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17. Other methods to prepare MgO NPs
Mg(NO3)2. 6H2O were dissolved in ethylene glycol solution and Na2CO3
was added into above mixture under sonication. Then it was filtered,
washed using water and dried. Finally, the samples were obtained through
calcination.
MgSO4.7H2O was dissolved in NH4OH and the mixture is constantly
stirring with deionized water and finally dried.
Mg(NO3)2. 6H2O and urea were dissolved in distilled water with
appropriate molar ration and the above mixture under were stirred for 15
min. Then kept at microwave oven. The obtained powder was washed
using distilled water and dried.
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18. Results and Discussion
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19. Characterization of MgO NPs
 X-ray Diffraction analysis
 FT-IR Spectrum
 High Resolution Transmission Electron Microscopy – (HR-TEM)
 UV– Vis Diffuse reflectance spectroscopy (DRS)
 Photoluminescence Spectroscopy (PL)
 Raman spectra
 Cytotoxicity – Cell Viability Assay
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20. X-ray diffraction patterns of MgO NPs
The average crystallite size, Debye-
Scherrer formula,

0.89
 cos

L 
L - Average crystallite size (nm)
λ - X-ray wavelength (nm)
β - full width at half maximum (FWHM)
θ - Bragg angle of the plane 20

21. HR-TEM images MgO NPs
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22. Diffuse reflectance spectra (DRS) of MgO NPs
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23. FT-IR spectra of MgO NPs
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24. Raman spectrum of MgO nanoparticles
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25. Room temperature PL spectra of MgO NPs
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26. Cytotoxicity of MgO NPs against various cells
(a) Normal human lung fibroblast CCD-25Lu cells,
(b) HeLa cells,
(c) SNU-16 cells and
(d) AGS cell lines treated for 24, 48 and 72 h respectively.
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27. • The cytotoxicity results of MgO NPs against cancer cells are displayed in the
Figure.
• Fig 4(a) shows that the toxicity of MgO NPs against normal fibroblast cells was
observed even at higher concentrations of MgO (300 g ml⁻1).
• It was evident from Fig. 4(b)–(d) that the cancerous cells were more sensitive to
MgO NPs.
• The figure shows both dose dependent and time dependent toxicity of MgO NPs
towards cancer cells.
• These results suggest that MgO can effectively kill the cancer cells in a dose
dependent manner in 24 h, and only a little difference in toxicity was observed
for 72 h.
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28. Generation of reactive oxygen species (ROS)
MgO + hv  e-cb
+ h+
vb
(MgO absorbs a photon of energy equal to or greater than its band gap width,
an electron promoted from valence band to the conduction band leaving
behind an electron vacancy or hole in the valence band.
If charge separation is maintained,
O2 + e-cb
 O2-. (superoxide radical anion)
H2O + h+
vb  OH. + H+
O2
-.and OH. – reactive oxygen species.
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29. MgO NPs induced apoptosis in AGS cells
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30. The cells treated with increasing concentrations of MgO NPs showed a
progressive accumulation of the apoptotic bodies (arrows) in a dose and
time dependent manner.
This illustrates the apoptosis mechanism of cell death occurring in
cancerous cells after exposure to MgO NPs.
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31. Conclusion
MgO NPs have been synthesized by a facile, low-cost, simple-precipitation
method.
MgO NPs are acts as an antimicrobial agent due to its high surface to
volume ratio and unique physico – chemical properties.
The cytotoxicity effects of MgO NPs towards cancer cells are both time
ands dose dependent.
MgO NPs are alternative to chemotherapy due to their toxicity levels
against cancer cells through apoptosis by ROS generation.
Nanotoxicity depends on electrostatic interaction between NPs with
membrane and accumulation in cytoplasm.
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32. References
 [1] Y. N. Chang, M. Zhang, L. Xia, J. Zhang, G. Xing, Mater. Rev. 5 (2012)
2871.
 [2] A. Chalkidou, K.Simeonidis, M.Angelakeris, T. Samaras, C. Martinez,
L. Balcells, K. Papazisis, C. Dendrinou, O. Kalogirou , J. Mag. Magn.
Mater. 323 (2011) 780.
 [3] M. A. Zolfigol, F. Shirini, G. Chehardoli, E. Kolvari, J. Molecular Catal.
A: Chem., 265 (2007) 272.
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