1. دکترعلی شاکری زاده پنجمین جلسه ژورنال کلاب
Graphene oxide-BaGdF5 nanocomposites for multi-modal imaging
and photothermal therapy
ارائه دهنده:
دکترعلی شاکری زاده

2. Introduction
As we all know, chemotherapy, radiotherapy and surgery are important therapeutic approaches for malignant tumors.
All cause strong side effects!!!
Photothermal therapy (PTT), as a novel method for cancer treatment.
Precise energy delivery to target tissue.
To date, a variety of nanomaterials, such as:
gold nanostructures,
palladium nanosheets,
metal sulfide nanoparticles,
tungsten oxide nanowires,
carbon nanomaterials (carbon nanotubes and nano-graphenes),
and various organic NPs
have been demonstrated to have potential PTT applications.

3. Introduction
Graphene oxide, a well known two-dimensional (2D) carbon material with excellent electronic, optical, thermal, and mechanical properties, has been extensively studied in the past decade.
Potential applications of graphene in biomedical fields:
nanocarriers for drug and gene delivery
biosensing platforms
molecular imaging agents
photothermal agents for tumor therapy
Considering their large surface area, graphene oxide (GO) nanosheets can be integrated with various types of NPs to form multifunctional nanomaterials for different application purposes:
Therapy
Imaging

4. Introduction
Nowadays, magnetic resonance (MR) and X-ray computed tomography (CT) imaging modalities are widely used for various experimental and clinical applications.
MR imaging is a noninvasive and nonionizing imaging method that can offer high sensitivity and good discrimination for soft tissues.
Gadolinium (Gd3+) metal ion based complexes (e.g. Gd-DTPA) are currently being used clinically as T1 relaxation agents due to their unique high spin paramagnetism.
However, MR imaging is not suitable for imaging in patients who possess magnetic hardware, and it also shows no signal for high density calcification.

5. Introduction
In comparison, CT affords better spatial resolution than other imaging modalities, and it could give high-resolution 3D anatomic structure information of tissues.
The clinically used iodine-based small molecular CT contrast agents are subject to severe limitations including short imaging time and renal toxicity.
New nanoparticulate CT contrast agents with high Z metal elements
Nevertheless, even if highly efficient CT agents were employed, the low sensitivity and poor resolution for soft tissue still limit the clinical application of CT technology.

6. Dual mode MR/CT imaging
Introduction
Dual mode MR/CT imaging
To satisfy the high requirements of efficiency and accuracy for the clinical diagnosis, combination of multimodal data is often required.
It is believed that the combination of MR imaging with CT modality could achieve more useful information of soft tissues or tumors with much enhanced accuracy.

7. This article

8. Experiments at a glance NPs Characteristics FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology

9. Methods & Results

10. Methods & Results EDS spectrum of nanocomposite
UV-vis-NIR absorption of:
GO (100 µg/mL)
GO/BaGdF5/PEG (100 µg/mL)
BaGdF5/PEG (500 µg/mL)

11. Experiments at a glance NPs Characteristics FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology

12. MR imaging of GO/BaGdF5/PEG in solution
Methods & Results
Magnetic sensitivity of GO/BaGdF5/PEG solutions was investigated on a 0.5 T MR scanner.
T1-weighted MR images were acquired with a conventional spin-echo sequence
The longitudinal relaxivity (r1) was measured to be 4.8 /mM x s which is higher than that of Gd-DTPA (3.5 /mM x s).

13. MR imaging in vitro Methods & Results
Hela cells incubated with different concentrations of nanocomposite was investigated on a 3.0 T system.
Incubation time: 4 h
ICP analysis for Gd3+

14. MR imaging in vivo Methods & Results
MR imaging in vivo was investigated with HeLa tumor-bearing nude mice.
Injection: (20 mg/kg body weight; i.v.)
Time-dependent brightening in the tumor
The signal intensity in tumor site increases remarkably by 3.7 times after injection for 24 h.
EPR effect

15. CT imaging of GO/BaGdF5/PEG in solution
Methods & Results
HU/mM

16. CT imaging in vivo Methods & Results
CT imaging in HeLa tumor-bearing mice using a small animal micro-CT system.
Images were taken 0.5 h after injection

17. Experiments at a glance NPs Characteristics FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology

18. In vitro cytotoxicity of GO/BaGdF5/PEG in Hela cells
(MTT assay)
Methods & Results

19. In vitro cytotoxicity of GO/BaGdF5/PEG in L929 cells
(MTT assay)
Methods & Results

20. Experiments at a glance NPs Characteristics FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology

21. Photothermal properties in solution
Methods & Results
Different concentrations were exposed to an 808-nm laser at a power density of 0.4 W/cm2 for 10 min.
time- and concentration-dependent temperature increase upon irradiation.
33 °C
No temperature variation for BaGdF5/PEG concentration even at 3 mg/mL.

22. Photothermal properties in solution
Methods & Results
The temperature of the solutions was monitored using an infrared thermal imaging system.
Infrared thermal images before and after 10 min of laser irradiation for GO/BaGdF5/PEG with the concentration of 200 mg/mL.

23. In vivo cancer PTT Methods & Results
Infrared thermal images of HeLa tumor-bearing mice with (a1) or without (a2) injection of GO/BaGdF5/PEG exposed
to 808-nm laser irradiation
(0.5 W/cm2) for 10 min
(24 h post-injection)

24. In vivo cancer PTT
Methods & Results

25. Experiments at a glance NPs Characteristics FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology

26. PTT of cancer cells in vitro
(MTT assay)
Methods & Results
(200 µg/mL)
0.4 W/cm2

27. PTT of cancer cells in vitro
(Flow cytometry)
Methods & Results

28. In vivo cancer PTT
Methods & Results

29. In vivo cancer PTT Methods & Results
PTT did not bring significant side effects

30. H&E-stained histology images of tumor
In vivo cancer PTT
Methods & Results
H&E-stained histology images of tumor
(a) PBS only, (b) laser irradiation only, (c) GO/BaGdF5/PEG only,
(d) both GO/BaGdF5/PEG and laser irradiation.

31. Conclusion Experiments at a glance NPs Characteristics
FTIR, UV-Visible, EDS,…
Diagnostics studies
MRI
In Solution
In Vitro
In Vivo
CT Scan
Therapeutic Studies
Cytotoxicity
Healthy Cells
Cancer Cells
PPT Studies
MTT
Flow cytometry
Tumor Size
Body Weight
Pathology
Conclusion

32. Conclusion GO/BaGdF5/PEG shows: good stability
low cytotoxicity even at high concentrations
Promising properties to be used as T1-weighted MR and X-ray CT duel-mode contrast agent
excellent photothermal behavior for in vivo photothermal cancer treatment
This nanocomposite may be further conjugated with different targeting ligands to construct multifunctional systems for targeted theranosis of cancers.