Photo dynamic therapy is old modality using up tel now.e this presentation will give lights on the PDT from the beginning up to date and overcome the disadvantages by using new modality of treatment by nanotechnology.

1. Nanotechnology implementation in
Photodynamic Therapy
By
Ghada Moneer Mostafa
Under supervision
Prof. Dr. Yasser Attia
NILS -CairoUniversity
2018

2. INDEX
• 1-Introduction
• 2- Photosensitizers
• 3-Nanoparticles in PDT
• 4-Applications
• 5-Conclusion

3. 1-Introduction
1.1-History of PD
1.2 -Mechanism of Action of PD
1.3-Photodynamic Action in the Body
1.4- Mechanisms of apoptosis

4. 1-Introduction
• 1st low of Photochemistry = states that light
(photons) must be absorbed to have an effect.
• Not change any other molecule in the system
Change another molecule in the system.
Photosensitizer (PS)
Photosensitization Process
Photodynamic Therapy (PDT)
(Three key components: a photosensitizer, a light source, and
tissue oxygen(Kim, Jung, and Park 2015).

5. Introduction
1.1 History of PDT
• The origins of light as a therapy in medicine and surgery
began in 3000 BC in Ancient Egypt and India ancient
Greece.disappeared for many centuries(Ormond and
Freeman 2013), (Abdel-kader 2014).
• 1890-Oscar Raab(acridine orange, Paramecium)
(Felsher 2003).
• 1903 -Von Tappeiner (eosin + irradiation).
• late 1970s- hematoporphyrin derivative (HPD)
(Kim, Jung, and Park 2015).
• Today the addition to many uses in imaging and
treatment has an impact on viruses , Fungi and bacteria
(Dai et al. 2010).
http://en.wikipedia.
org/wiki/File:Akhenaten_
as_a_Sphinx_%28Kestner_
Museum%29.jpg
(Felsher 2003).
(Dai et al. 2010).

6. Timeline; History of photodynamic therapy (1900-present)(Felsher 2003)

7. 1. Introduction
1.2 Mechanism of Action of PDT
Mechanism of action of photodynamic
therapy (PDT)(Felsher 2003)
Jablonski diagram showing the main events
leading to type I and type II photochemical
reactions, which eventually may result in
oxidative cell damage. S0, ground state of the
photosensitizer (PS); S1, first excited singlet
state of PS; S2, second excited singlet state of
PS; T1, first excited triplet state of PS; ISC,
intersystem crossing; 3O2, triplet oxygen; 1O2,
singlet oxygen(Ormond and Freeman 2013),
(Zhang et al. 2018).

8. 1. Introduction
1.3 Photodynamic Action in the Body
Schematic representation of photodynamic therapy (PDT)
treatment of a malignant tumor (Ormond and Freeman 2013).

9. 1. Introduction
1.4 Mechanisms of apoptosis
Some PDT-associated apoptosis pathways involving plasma membrane death receptors,
mitochondria, lysosomes and ER, caspases, and Bcl-2 family proteins. (Oleinick, Morris, and
Belichenko 2002).

10. 2- Photosensitizers
2.1- First generation PSs
2.2-Second generation PSs
2.3- Strategies for designing new
generation PSs
2.4- Recent development in anticancer PSs
2.5- Photosensitizer Distribution in Tissues

11. 2. Photosensitizers (PSs)
• 2.1 First generation PSs
• 2.2 Second generation PSs
Basic structures of
porphyrinoid photo-
sensitizers(Ormond and
Freeman 2013)
Structural skeletons
of several anticancer
PSs(Zhang et al.
2018)

12. 2. Photosensitizers (PSs)
• 2.3 Strategies for designing new generation PSs.
• 2.4. Recent development in anticancer PSs
Chemical structures of porphyrin-type PSs 1 - 7 (Zhang et al. 2018).

13. 2. Photosensitizers (PSs)
2.4. Recent development in anticancer PSs
Chemical structures of chlorin-type PSs
8–14 (Zhang et al. 2018).
Chemical structures of phthalocyanine-type
PSs 15–22(Zhang et al. 2018).

14. • Inside the body, PS interact with tumors via low-
density lipoprotein (LDL) receptors.
• PS solubility is important factor in its distribution
and location inside tumor cells.
• charge of PS, Cationic compounds found in mitoch-
ondria, while anionic species found in lysosomes.
• (Ormond and Freeman 2013).
2. Photosensitizers (PSs)
2.5. Photosensitizer Distribution in Tissues

15. 3-Nanoparticles in PDT
• 3.1-Synthesis of Nanoparticles
• 3.2- Biosynthesis Mechanism of green
nanoparticles
• 3.3- Example of an Application of green
synthesis gold nanoparticles

16. Nanotechnology
• Nanotechnology is an exciting tool to design
different types of particles
• a diameter smaller than 100 nm.
• unique properties -->>a vast application in the
field of medicine, diagnostic, imaging, drug
discovery, tissue engineering …etc. (Mc Carthy et
al. 2015), (Rawat et al. 2006),(Bhattacherjee, Ghosh, and
Datta 2018) (Abhilash 2010).

17. Different Types of Nanocariaress (Rawat et al. 2006).
Nanoparticles

18. Nanoparticles
Different types of nanoparticles commonly used for biomedical applications
and which offer significant potential in delivering therapeutics across the blood
brain barrier (Mc Carthy et al. 2015).

19. 3. Nanoparticles in PDT
3.1 Synthesis of Nanoparticles
Generalized flow chart of various physico– chemical approaches of nanoparticles
synthesis with highlighting of biological synthesis(Hussain et al. 2016).

20. 3. Nanoparticles in PDT
3.2 Biosynthesis Mechanism of green nanoparticles
Diagram summarizing the possible
mechanism of biologically mediated
synthesis of nanopar-ticles. M metal
salt, M+ Metal ion, Mo neutral atom
(Hussain et al. 2016).

21. Table : Biological entities which synthesize metal oxides nanoparticles with their
size, shape and brief experiments
3. Nanoparticles in PDT
3.2 Biosynthesis of green nanoparticles

22. • (Bhattacherjee, Ghosh, and Datta 2018), There work about
Green synthesis and characterization of antioxidant-tagged
gold nanoparticle (X-GNP) and studies on its potent
antimicrobial activity.
3. Nanoparticles in PDT
3.3 Application of green synthesis gold nanoparticles
Size and charge distrib-
ution: Determination of
size and surface charge of
synthesised nanoparticles
(GNP and X-GNP): (a)
Dynamic light scattering
(DLS) analysis of GNP and
X-GNP suspension. (b)
Estimation of surface
charge of GNP and X-GNP
by zeta potential
measurement.

23. Batch growth profiles of P. aeruginosa (a), E. coli (b), M. luteus (c), A. lwoffii (d) and B.
subtilis(e) with 25% supplements of GNP and X-GNP. NB (Nutrient broth, pH 7.0) with
fraction-X was taken as(+) ve control and NB without any supplement was taken as (-) ve
control. The maximum percentage of growth inhibition (f) with 25% supplements of
fraction-X, GNP and X-GNP was plotted after 24 h of incubation at 37 _C.

24. • (Attia et al. 2016),their study based on the chemical methods
for the synthesis of gold nanoparticles lead to the formation
of some toxic chemicals adsorbed on the surface that may
have adverse effects on their medical applications.
3. Nanoparticles in PDT
3.3 Application of green synthesis gold nanoparticles
Scheme The nature of the interaction between the charged NPs
with butane-2,3-diol and indole-3-acetic acid.

25. . Cytotoxicity of yeast, Au–citrate NPs
and Au/yeast nanocomposite samples
against Ehrlich Ascites Carcinoma
(EAC) cells in dark and visible light
incubation (Attia et al. 2016).
Ehrlich ascites carcinoma cells in control,
yeast extract, Au–citrate NPs and Au/yeast
nanocomposite samples in dark and light
incubation for 1 h (Attia et al. 2016).

26. 4.ADVANTAGES OF USING GREEN
NANOPARTICLES IN PDT

27. 4- Applications of Greennanoparticles in PDT
• (Chien et al. 2018) study the effect Folate-Conjugated
and Dual Stimuli-Responsive Mixed Micelles Loading
Indocyanine Green for Photothermal and
Photodynamic Therapy.
• folic acid is a specific cancer cell recognition.
• carboxylic acid on folic acid regulate the pH-dependent
thermal phase transition of polymeric micelles for
controlled drug release.

28. Cumulative ICG release from MM3
micelles at different pH (Chien et al.
2018).
CLSM images of HeLa
cells treated with free
ICG and ICG-MM3
micelles for 4 or 24 h
with or without NIR
irradiation (1.2 W cm−2,
irradiated for 4 min).
Scale bar: 25 μm (Chien
et al. 2018).

29. CLSM images of HeLa cells treated with a) free ICG, b) ICGMM3 micelles, c) ICG-
PTN micelles, and d) MM3 micelles under NIR irradiation (1.2 W cm−2,
irradiated for 4 min) for ROS detection using DCFH-DA. Scale bar: 25 μm. e)
Average DCF fluorescence intensity of the CLSM images in each sample, analyzed
by ImageJ software. Data are presented as mean ± standard deviation (Chien et
al. 2018).

30. • (Maruyama et al. 2015), they study the treatment
effect of near-infrared photodynamic therapy using a
liposomally formulated indocyanine green derivative
for squamous cell carcinoma.
• The result of that work showed that cell death and
apoptosis were only observed in the PDT group
receiving LP-ICG-C18. LP- ICG-C18 itself had no
cytotoxic activity and showed good biocompatibility.
4- Applications of Greennanoparticles in PDT

31. The cell morphology 96
hours after irradiation. (A)
LP-ICG-C18 without
irradiation. (B) LP-ICG-C18
with irradiation. (C) ICG
without irradiation. (D) ICG
with irradiation.
(E)DMEMwithout
irradiation. (F)DMEM with
irradiation. (G) LP without
irradiation. (H) LP with
irradiation. (I) In vitro
cytotoxicity comparison
with DMEM without
irradiation. “(-)” is without
irradiation and “(+)” is with
irradiation (Maruyama et
al. 2015) .
“*” represents P<0.05 since
96 hours after irradiation .
Data are presented as mean
± SD (n = 3) (Maruyama et
al. 2015).

32. 5-Conclusion
• PDT is a treatment modality from ancient times.
• The different studies that have been performed
throughout the years have led to its development and given
us the PDT we know today.
• It is now considered a promising, less invasive treatment
method of malignant and premalignant diseases and has
been approved for the treatment of certain types of
neoplasms.
• The discovery of novel PS molecules with desired
pharmaceutical properties and the application of novel PS
in clinical trials are challenging tasks.

33. • the association of classical PSs to different carriers has also
been explored to improve their photophysical properties
and/or their targeting to tumors.
• On one hand, antibodies, receptor ligands, and other
targeting molecules have been used to actively increase the
accumulation of PSs in tumors.
• On the other hand, different nanostructures have been
used to enhance or to maintain the activity of PSs in
aqueous media, and to actively and/or passively deliver
these molecules to tumors. Both of these systems, and
even combinations of them, have been referred to as the
third generation PS.