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Prof. Dr. Emad A. Al-Ashkar

Head of LASER Group, Center of Excellence &

Spectroscopy Department

National Research Centre

Nanogold in Cancer Therapy

Nanomaterials

Nanomaterials describe, in principle, materials of

which a single unit is sized (in at least one

dimension) between 1 and 1000 nanometers

(10−9 meter) but is usually 1—100 nm (the usual

definition of nanoscale).

Nanotehnology

Nanotechnology: is the manipulation of matter at the atomic

and molecular scale to create materials with new and

advanced properties.

This definition reflects the fact that quantum mechanical

effects are important at this quantum-realm scale, and so

the definition shifted from a particular technological goal

to a research category inclusive of all types of research and

technologies that deal with the special properties of

matter that occur below the given size threshold.

Nanotechnology integrates different fields including, physics, chemistry, biology, medicine and engineering in order to help and advance quickly the world of medicine

Nanotehnology

Impact of AuNPs on cancer cells. Size, morphology, functional groupson the AuNP surface and the cell type determine the subcellulardistribution of AuNPs. AuNPs can cause tumor cell death by photo-thermal ablation, mechanical damage, and increase in the localized drug concentration. These events can be combined to enhance their killing efficiency.

Au Nanotehnology

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Hollow AuNS

Some Different Shapes of Gold NPs

Au nanoparticles Au nanorods

Au nanostars Au nanoflowers Coated Au nanorods

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Silver coated gold nanorods

Some Different Shapes of Gold NPs Cont.

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Au nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photo-thermal agents, contrast agents and radio-sensitisers

Gold Nanoparticle

Nano-devices

PTT (Photothermal Therapy)

uses near-infrared (NIR) laser light-generated heat to destroy tumor cells.

LSPR (Localized Surface Plasmon Resonance)

Photons can couple to the plasmon resonance of theconduction electrons at the surface of AuNPs to producetheir collective oscillation (Time-dependant).

Au colloids are a promising platform for many

biomedical applications.

Use of Au NPs in medicine

Diagnostic Applications

Therapeutic Applications

-With Energy Source (LASER)

-Alone

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Range of surface plasmon resonances of Au NPs as a function of their shapes.

LASER wavelength must be matched

with AuNPs absorption

Cellular Internalization

• Once the nanoparticle has safely transported to its target organ, it binds to the tumor cell

• Selective Treatment

Biological Window

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PEG-coated AuNPs

Au

Me

SS

Me

S

Me

S

Me

S

Me

Me

S S

Me

OO

CH3

SH n

mPEG-SH

Capping Density

Polymeric Delivery Systems in PTT

Preparation of Au NRs in NRC

Some Figures of NRC works related to Au NRs

Lab. Animals

Tissue Distribution and Efficacy of Gold NanorodsCoupled with Laser Induced Photoplasmonic

Therapy in Ehrlich Carcinoma Solid Tumor Model

M. A. El-Sayed, A.A. Shabaka, O.A. El-Shabrawy, N.A. Yassin,S.S. Mahmoud, S.M. El-Shenawy, E. Al-Ashqar, W.H. Eisa, N.M. Farag,

M.A. El-Shaer, Nabila Salah, Ahmed M. Al-Abd

PLoS ONE, 2013, 8(10): e76207 doi:10.1371/journal.pone.0076207

Some Figures of NRC works related to AuNRs

Physical properties of GNRs. TEM image of GNRs with Plasmon band energies at 800 nm (A) and UV Visible NIR absorption spectra of the AuNRs (B) prepared using single surfactant mixtures. Scale bar = 100 nm.

Histological examination for EACC solid tumor treated with Au NRs coupled with laser induced photo plasmonicthermal therapy. EACC tumors of control group (A); Au NRs IT treated group (B); and IV treated group (C) were stained by H&E regular stain. AuNRs coupled with PTT showed massive tissue destruction appeared as non-cellular debris eosinophilic areas (arrows) Scale bar = 20 μm

NRC Gold Nano-Rods (Au NRs)

Antitumor activity of GNRs coupled with laser induced photo plasmonicthermal therapy in EACC solidtumor bearing mice. EACC tumor bearing mice were given GNRs (1.5 mg/kg every three weeks) by I.V. (▲) and I.T. (■) administration compared to PBS treated animals (●). Animals were exposed to laser plasmonic beam (50 W/cm2 for 2 min) every week. Tumor size was measured every three days andplotted (A). Representative tumors are shown in panel (B). Data are presented as mean ± SEM (n=10).

NRC Gold Nano-Rods (GNRs)

Tissue pharmacokinetics of AuNRs after I.V. and I.T. administration to EACC tumor bearing mice. GNRswere administered by I.V. (◌) or I.T. (●) injection (1.5 mg/kg) to tumor bearing mice. Tissue concentration of gold in tumor (A), liver (B), spleen (C), and kidney (D) tissues were assayed for Gold content at different time intervals until two weeks. Data are presented as mean ±SEM (n=3)

NRC Gold Nano-Rods (GNRs)

AuNRs administered systemically was equally distributed to Ehrlich carcinoma solid tumor tissues compared to intra-tumoraladministration of AuNRs. In addition, systemically administered AuNRs were equipotent to local intra-tumoral administered AuNRs when coupled with laser plasmon thermal therapy in inducing tumor growth arrest. Finally, accumulation of AuNRs in vital organs such as liver and spleen apparently was non-toxic;however, might warrant further toxicological detailed studies. Further formulations of better surface plasmon characteristics and less accumulation kinetics in vital organs might pave promise in the field of laser-induced photo plasmon thermal therapy of solid tumors. It is recommend for the current AuNRs formulation to be considered for clinical assessment in solid tumor treatment coupled with laser photoplasmonic therapy.

Conclusions of That Work

Some Examples of NRC works related to AuNRs

Big Animals Got Cancer Normally

Normal Pregnancy and Lactation in a Cat after Treatment of Mammary Gland Tumor When Using

Photothermal Therapy with Gold Nanorods: A Case Report

Abdoon AS, Al-Ashkar EA, Shabaka A, Kandil OM, Eisa WH, Shaban AM, Khaled HM, El Ashkar MR, El Shaer M, Shaalan AH and El Sayed MA

J Nanomed Nanotechnol, 2015, 6 (5), 1000324ISSN: 2157-7439 JNMNT, an open access journalImpact factor:4.7

One of the many studies done

Not our work

-AuNPs are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic.-They protects drugs from being degraded in the body before they reach their target-Enhance the absorption of drugs into tumors and into the cancerous cells themselves-Allows for better control over the timing and distribution of drugs to the tissue, making it easier for oncologists to assess how well they work-Prevent drugs from interacting with normal cells, thus limiting side effects

Advantages of Au Nanotechnology

-Since these particles are very small, problems can actually arise from the inhalation of these minute particles (in solid form), at least, much like the problems a person gets from inhaling minute asbestos particles -Au NPs requires High purity materials as well as highly specialized man power-They require expensive investigations (dimensions, shape, homogeneity,…..) -The stability of AuNPs have always a question mark -The repeatability of the sample is sometimes difficult-Clearance of the drug-Presently, nanotechnology is still expensive, If produced in mass production, the unit cost will be reduced

Disadvantages of Au Nanotechnology

In recent years, the U.S. Food and Drug Administration (FDA) has approved numerous Investigational New Drug (IND) applications for nano-formulations, enabling clinical trials for breast, gynecological, solid tumor, lung, mesenchymal tissue, lymphoma, central nervous system and genito-urinary cancer treatments.

Where Nanotechnology Stands Now

ReviewOff to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

M. Kodiha, Y. M. Wang, E. Hutter, D. Maysinger, U. Stochaj

Theranostics 2015, Vol. 5, Issue 4, 357-370http://www.thno.org

Important Review Article

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