Role of metallic nanoparticles in managing brain tumor “glioblastoma”

*The general definition of nanotechnology is the creation and use of materials that have dimensions in the range of 1–100 nm.*Drug delivery is the most popular

use for nanomaterials.*glioblastoma are tumors of astrocytes

the star-shaped cells “glue-like”*highly aggressive

NPs can be used as : Vehicle for delivery. Contrasting agent “imaging”

MRI CT, flourescent QDs. Therapeutic agent “metallic

NPs”. Diagnostic tool . Multi-drug delivery .

NPS applications for brain tumor

Can iron kill cancer???

metallic NPs that can be heated with light or radiofrequencies, or by a magnetic field for thermal ablation of tumors “hyperthermia”.

many still require a greater understanding of their clearance and safety.

non biodegradable NP to be able to be excreted it must have a diameter less than the renal filtration cutoff of approximately 5–6 nm.

Fe3O4 NPs have shown success with antibody treatments as well as with thermotherapy induced by an alternating magnetic field.

Fe3O4 can be coated with polymers, liposomes, dendrimers and hydrogels .

Studies showed success in using an external magnetic field to guide a polymer Fe3O4 NP gene delivery system across the BBB.

Examples for therapeutic metallic NPs

Au “gold” NPs have the advantages of relatively straightforward synthesis, easy surface functionalization, small sizes, and the corresponding ability to be excreted by the body and remain relatively nontoxic.

Au NPs can also utilize thermotherapy by heating gold with visible, infrared, or radiofrequency pulses to cause localized tumor damage.

NPs can also allow loading of additional drugs for simultaneous multidrug delivery or even the addition of imaging probes for in vivo monitoring or diagnosis.

contrast enhancement by magnetic NPs used for MRI and contrast enhancement by AuNPs for computed tomography imaging .

Diagnostic NPs

Fe3O4 NPs :◦ The first NPs created for brain tumor imaging were

monocrystalline Fe3O4 NPs, which were conjugated to tumor-specific monoclonal antibodies called L6.

◦ Fe3O4 NPs with diameters around 50 nm have been shown to be relatively nontoxic and also biodegradable.

Gadolinium NPs : - gadolinium NPs showed high retention

time in tumor with relatively less toxicity than non-nanoparticulate gadolinium

Examples for metallic NPs used as MRI contrasting agent

QDs are highly advantageous as they can be tailored for fluorescence emission , QDs can potentially be toxic if accumulated in normal tissues without organic polymer protection.

Coprecipitation solution technique : - mixtures of mixtures of ferrous and ferric

hydroxides are oxidized using a mild oxidant (nitrate ions) in basic media followed by thermolysis under high temperature .

- The size of the particles can be controlled by the velocity of thermal reaction and concentration of the iron salts.

- The smallest particles can also be generated after adding polyvinylalcohol (PVA) to the iron salts.

- Modifications on this method allow synthesis of biocompatible magnetic nanoparticles in the presence of dextran or any other biocompatible polymer.

The Synthesis of metallic NPs

Aerosol/vapour methods: - spraying a solution into a series of reactors

where the aerosol droplets undergo evaporation of the solvent and solute condensation, followed by drying and thermolysis of the precipitated particle at higher temperature.

- In spray pyrolysis, the ultrafine particles are usually aggregated into larger particles, while in laser pyrolysis the ultrafine particles are less aggregated due to the shorter reaction time.

Facilitates functionalization Protects the drug from the body Protects the body from the drug Mantains physical properties of the drug

coating metallic NPs

A major hurdle in successfully treating brain cancer is the presence of the selective barrier between brain tissue and the blood.

However, it is important to note that the presence of a brain tumor disrupts this very selective BBB, and creates an opportunity for the improved delivery of therapeutic agents.

NPs take advantage of the enhanced permeability and retention effect to accumulate particles and/or drugs over time due to leaky vasculature and an ineffective lymph system for cancer .

Strategies of Overcoming the BBB:

1- Systemic Delivery: - Intravenous injection is the most widely

used method to deliver nanoparticles to the brain because of its non-invasive nature .

-Nanoparticle delivery is hindered because of clearance by phagocytes .

-To circumvent this, nanoparticles smaller than 100 nm are coated with poly (ethylene glycol) (PEG) which mitigate macrophage recognition and increase blood circulation half-life.

Routes of delivery

2- Local Delivery : Local or direct bolus injection of

nanoparticles intracranially is an alternative delivery method that bypasses the systemic circulation and BBB altogether.

A major disadvantage of this delivery technique stems from the tightly packed cells in the brain matter that results in low diffusion coefficients and causes sluggish diffusion and backflow of the injected nanoparticle .