Till now the development in surgery & other therapies doesnt give result needed for the cure of brain tumor but nanotubes is a technology transfer because it can help both preoperative & intraoperative brain tumor detection for diagnosis & also can target delivery devices for chemotherapy, gene therapy, photodynamic therapy & thermotherapy. The novel technology in diagnosis & treatment increases the management of brain tumor; so the promise of nanotechnology is the synthesis of ultra-small particles with a diameter of 10-200nm & the first achievement done is the imaging of gliomas which is a type of cancer develop in glial supporting nerve cells of the brain & otherwise the only test used to find a brain tumor is brain scanning. There are two types of brain tumor, primary & secondary; primary brain tumor starts in the brain but secondary brain tumor reaches the brain through blood due to the presence of other cancer type in the body as cancer of lung, breast, kidney, stomach, bowel (colon) & skin.
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Nanoparticles can carry many compounds to brain tumor as MRI (magnetic resonance imaging) contrast agents, chemotherapeutic agents & photosensitizers via a variety of chemical methods including encapsulation, adsorption & covalent linkage. Also the efficiency of nanoparticles can be enhanced by size & surface chemistry. Also the nanoparticles can be amplified by carrying many drugs at the time. Also the specificity of nanoparticles can be enhanced by the attachement of specific targeting modalities via a concept of "surface mediated multi-valent affinity effects".
The nanotubes in this experiment will target the angiogenic cells which are responsible for the blood vessels formation in brain tumor & theses nanotubes can be enhanced & targeted the brain tumor by adding poly-ethylene glycol (PEG) as a hydrophilic macromolecules at the surface of nanoparticles which cause the accumulation of these nanotubes in tumor tissue long after serum rejection due to the enhanced permeability & retention (EPR) effect of macromolecules.
This means that the serum delivered is isolated from the surrounding environment & also other pros of nanotubes that help us to avoid the toxicity of chemotherapeutic agents by encapsulation. Thus, the delivery of these drugs will be in high concentrations direct to tumor. So these assumptions permit to re-examine the developed drugs which were removed due to their dangerous side effects.
Nanotubes contain peptides, cytokines (large peptides), drugs, monoclonal antibodies (large peptides), ferro-magnetic agents to target cell surface markers as receptors on angiogenic cells through the phage display technique such as F3 peptide in nanotubes target nucleolin receptors expressed in proliferating angiogenic tumor cells & the nanotubes will be called F3-targeted nanoparticles & can carry both MRI contrast agents & photosensitizers; another example is chlorotoxin isolated from scorpion venom in nanotubes target chloride channels on the surface of glioma cells carrying MRI contrast agents & optical near IR dye. Another example is IL-13 doxorubicin-targeted nanovesicles can carry high drug concentrations. Another example is methotrexate-targeted nanoparticles target folate receptors and so on.
MRI (magnetic resonance imaging) is one of the applications of nanotechnology to manage brain tumors. Designing nanoparticles containing single or multiple iron oxide with or without the shell of organic material as PEG; iron oxide used as contrast agent to enhance MRI by influencing of endocytosis the MR signal intensity change but PEG is used to delay the presence of nanoparticles in the tumor parenchyma and this will be controlled by changing the length of PEG chains.
Gadolinium-based contrast agent & nanoparticles-based contrast agent both pass through BBB (Blood brain barrier) but the convention drug doesn't pass the BBB; the gadolinium & nanoparticle differ in their way of interaction. Standard gadolinium chelator image area of cleavage BBB only but iron oxide nanoparticle can enter the tumor cell by phagocytosis & image the tumor margin. Gadolinium diffuse freely through tumor but iron oxide nanoparticles has low diffusivity so it can be kept longer in tumor parenchyma.
Here the step of drug delivery, pegylated immunoparticles is the achievement of colloidal drug carriers to target brain tumor; these nanoparticles can carry drug to brain parenchyma from blood through receptor mediated transcytosis without causing damage to BBB. But the pEG chain must have some modification if it will go to carry drug. Drug is a protein so the covalent binding of protein ligands with PEG chain must be avoided so it will be modified at their free end to mPEG-PLA (methoxy PolyEthylene Lactide acid) which will be synthesized by ring opening polymerization starting from hetero-bifunctional PEG & lactide. These modifications also sustained the release of drug in tumor & that's the problem solved of the side effect of immunoliposomes.
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The drug used in this method is photofrin is a type of photodynamic therapy. Free photofrin can cause damage to healthy tissue but that solved by being encapsulated into nanoparticles to go directly to tumor brain. While activating by specific laser light, photofrin collapses the vasculature of tumor blood vessels which stops the blood flow from tumor which needed to survive. This method could eliminate a side effect of photodynamic therapy is that the healthy tissue become sensitive to light. Also the combination of drug with contrast agent can help to identify next dosage needed to treat effectively this tumor in the next administration.