Nanotechnology Applications in Cancer Diagnosis and Therapy

Transcription

1 Lecture XXVIII Nanotechnology Applications in Cancer Diagnosis and Therapy Abstract: Nanotechnology applications have reached exciting new area in science, with diverse applications in medicine. Nanotechnology has ability to detect particular affected tissue or cells and has potential to deliver drug only to those cells or tissue that are affected-this specificity makes nanotechnology to have wide range applications. This lecture seeks to outline the role of nanotechnology in different areas such as diagnosis of diseases, drug delivery and imaging etc.

2 Introduction Nanotechnology is science of study characters of material at nano scale and fabricate devices at this scale of length. On nano scale, there is vastly an increase in ratio of surface area to volume. Due to this, materials at nano scale show very different compared to what they exhibit on micro scale. For example gold which is inert normally can show chemical catalytic properties at nano scale. With the studies made on materials at nano scale there was a foreseen chance of development at every field. Nanoparticles were structured to be used for many purposes in many sectors. The nanoparticle drug delivery systems and diagnostic agents were promising tools for therapy of wide range diseases. Cancer Cancer is one of most dangerous chronic diseases which is now a plaguing problem throughout the world. Cancer is caused by the damage of genes which control the growth and division of cells, and thus these cells with altered genes lose control over cell division. There are over 200 types of cancers prevailing today. Everyday scientists are trying for a new way to deal with this fatal disease. The use of nanoparticle drug delivery system has shown better and promising ways to detect and kill the cancer cells. Nanoparticles are now being used in both diagnosis and treatment of some types of cancers and efforts are being made to fabricate more efficient and effective ways. Nanoparticle detection and treatment: Nanoparticles are of a few of nm and the cells are of the size of few microns. So nanoparticles can enter inside the cells and can access the DNA molecules/genes and, there is a possibility that the defect in the genes can be detected. Certain nano particles can be designed to absorb preferentially certain wave length of radiation and gets heated. Such a NP if enters in the cancerous cell will burn it if irradiated by suitable wavelength radiation. This is kind of the analogue of radiation therapy. Nanotechnology can be used to create therapeutic agents that target specific cells and deliver toxin to kill them. The NP will circulate through the body, detect cancer associated molecular changes, assist with imaging release a therapeutic agent and then monitor the effectiveness of the intervention. Brain Cancer Tumor formations found intracranial within the brain or central spinal canal correspond to Brain tumor. These are formed by uncontrolled cell division in intracranial parts like brain, blood vessels, in the cranial nerves pituitary gland, pineal gland. Some of these tumors might be cancerous that is malignant. Brain tumors may cause serious problems or may be even fatal because of its invasive and infiltrative character in the intracranial cavity.

3 The diagnosis and treatment of brain tumors are very difficult due to the Blood Brain Barrier (BBB), which restricts the passage of molecules and substances from passing it and reaching the brain. Therefore for the tracers to reach the tumor spot BBB must be disrupted. Nanoparticles used for diagnosis They factor for treating a tumor is to deliver the effective concentrations of tracer agents (for detection) and therapeutic agents to the tumor site. Nanoparticles are selected for this job cause with them there are advantages like control on releasing the agents, molecular targeting, camouflage (avoiding immune response) etc. Varieties of nanoparticles are designed for MRI, PDT and chemotherapy. The main part of designing a nanoparticle involves its ability to pass through the Brain blood barrier. This is accomplished by coating the nanoparticle with hydrophilic polymers which help them overcome the reticuloendothelial system uptake. Magnetic Resonance Imaging (MRI) is an imaging technique used to visualize the internal body parts in detail. MRI involves the use of contrast agents, which are injected into the body, thus enhance the imaging of the internal body structures. Currently gadolinium based contrast agents are used. But recently Iron Oxide nanoparticles are also proven to be excellent contrasting agent for MRI imaging. The iron oxide contrast agents are termed as Super magnetic iron oxide (SPIO) or ultra small super magnetic iron oxide (USPIO), depending on the size of the nanoparticles. These nanoparticles have been approved for using them in detection of liver and spleen diseases and efforts are being continuously made to improve their efficiency and to extend their application to central nervous system imaging. The USPIO consists of a 5-6nm iron oxide surrounded by dextran coating to give a hydrodynamic diameter of 20-30nm. An in vivo study of dextran coated iron oxide nanoparticles showed after intravenous administration, most of the agents were localized in liver, spleen and lymph nodes. The accumulation in the brain tumor was low but was 10 times higher than brain tissue other than the tumor which showed a significant differentiation of the tumor. Unlike the Gd contrast agents which show immediate enhancement and decreases within hours, the USPIO gradually increase to a peak in hours and showed a sharp difference between tumor and normal cells. The studies showed that iron oxide agents would not replace conventional gadolinium-enhanced MR imaging but could add additional information especially in identifying the inflammatory component and compromised blood brain barrier involved in infiltrating malignant brain tumors.

4 Schematic diagram of magnetic nanoparticles. Left: Iron oxide core surface right: coated with polymer; nanoparticle with incorporated iron oxide. Reference: Advanced Drug Delivery Reviews, Volume 58, Issue 14, 1 December 2006, Page 1563 Nanoparticles are further improvised for imaging the tumor tissue during both the pre-surgical planning phase and surgical resection phase. During a surgery it is difficult to distinguish the tumor tissue from the normal tissue, and any cancer cellss left behind are likely to proliferate and form new tumors. This problem is solved by devising a dual probe nanoparticle which contains a iron based nanoparticle tagged with near infrared fluorescent (NIRF)) molecule Cy5.5. The fluorescent moleculee was either conjugated to the amine-functionalizeis linked to the iron oxide core. When the tumor is dextran coat on the surface or to the amine terminated PEG that exposed during the surgery a NIRF imaging is done and the location of tumor or the traces of tumor are detected for complete attenuation. The NIRF imaging showed significant results when compared to the Green fluorescence protein imaging. Nanoparticles for Treatment Chemotherapy in the case of brain tumor showed feasible results due to low permeability of most anti-cancer agents through BBB. The nanoparticles with their advantages of ability to travel through the BBB emerged as a promising tool. Many nanoparticles have been devised for chemotherapy and have also been adopted. Solid Lipid Nanoparticles (SLN) loaded with two anti-tumor drugs have been investigated as potential drug carriers to the brain. Paclitaxel(an active chemotherapeutic agent ) was loadedd onto SLN and tests were carried out in vivo and in vitro. The SLNs were assembled by microemulsion technique using emulsifying wax as oil phase, water and Brij78 as surfactant. In vitro cytotoxicity tests with paclitaxel loadedd SLNs as well as with a commercially available Taxol formulation containing paclitaxel weree performed using two different cell lines U-118 and HCT-15. While U-118 showed no difference in growth, HCT-15 cell growth was significantly decreasedd in the presence of paclitaxel nanoparticles when compared to free paclitaxel. This results show that the nanoparticle drug delivery system were positive with overcoming the BBB and paclitaxel brain uptake was increased. Also SLNs loaded with Doxorubicin showed better

5 results when compared to normally injected doxorubicin n. Doxorubicin is a chemotherapeutic agent that inhibits DNA and RNA synthesis as well as cleaves DNA. The doxorubicin SLNs showed 5-7 fold increased in uptake of the drug than normally injected doxorubicin. Polybutylcyanoacrylate (PBCA) Nanoparticles have beenn reported to achieve successful delivery of various drugs to the brain with the help of surface-coated surfactant. Polysorbate 80 was found to be most efficient surfactant among many others tested. These nanoparticles are loaded with doxorubicin and tested by intravenous introduction into healthy rats. Results showed that these nanoparticles produced very highh concentrations of doxorubicin in brain when compared to normally injected drug. Photodynamic therapy (PDT) is a form of phototherapy using nontoxic light-sensitive compounds that are exposed selectively to light, whereupon they become toxic to targeted malignant and other diseased cells. Nanoparticle based PDT has the same advantages of nanoparticle chemotherapy. Nanoparticle based PDT is investigated using Polyacrylamide (PAA) nanoparticles. Multifunctional nanoparticles withh both MRI and PDT advantages have been designed, whichh has a PAAA nanoparticle core and carries the following components: 1) PDT agent (Photofrin) 2) MRI-detectablee contrast agent (iron oxide); 3) vascular-targeting ligand (F3 peptide or RGD peptide). Photofrin is a photosensitizer. Schematic drawing of the redox responsive nano PDT agent. Fluorescence and singlet oxygen generation (SOG) are quenched in the native state. When the nanoparticles enter cancer cells via endocytosis, disulfide bonds are cleaved by intracellular reductive agents, resulting in dequenching of fluorescence and SOG.. Reference: J. Mater. Chem. B, 2013, 1,429 BREAST CANCER Breast Cancer is a type of cancer originating from breastt tissue and spread to other tissues in the body. Breast cancer starts usually in the ducts or lobes that supply milk. Most common breast

6 cancer is ductal carcinoma that begins in the lining of milk ducts. Another type is lobular carcinoma that starts in the lobules of the breast. Invasive breast cancer is the cancer in which it spreads to other tissues in the body from where it starts either in ducts or lobes. It occurs mostly in women, male breast cancer can also occur but it is very rare. Survival rates depend on the type of cancer, stage, treatment, geographical location of the patient. Generally it is not more than 5 years after diagnosis. Sources says that "More than 180,000 women could die from breast cancer by 2030 unless action is taken over critical gaps. USE OF NANOBIOTECHNOLOGY IN DIAGNOSIS AND IMAGING OF BREAST CANCER: Nanobiotechnology which is the biomedical application of nano sized systems. This helps in detection, imaging and treatment of disease.for this we can advantage that many receptors are over expressed during cancer conditions on the cell, for example: oestrogen receptor, progesterone receptor,erbb2. Based on these receptors therapeutic decisions are made. Nanoparticles conjugated with different specific antibody or aptamers or peptide sequence can be used for detection and imaging of tumours. The success of diagnosis and treatment depends on the expression of receptors on the cancerous cells. Immunohistochemistry is one of the best methods in order to determine about the hormone receptors.in place of Nanoparticle Quantum dots are used because they have ability to eject light without any form of photobleaching.different Quantum dots are attached to different antibodies and they are targeted to specific proteins so that the emitted from different quantum dots so that detection is possible.based on brightness or the level of fluorescence we can conclude about the level of toxicity. USE OF NANOPARTICLES IN TREATMENT OF BREAST CANCER: Tumour-selective delivery of anticancer agents is desirable to increase the cell-kill effect,while protecting the healthy tissue from exposure to a cytotoxic agent, thereby reducing systemic toxic effects, and nanoparticles could be used for this purpose. Agents like liposomal anthracycline, NAB paclitaxel and tamoxifen are most active agents in treatment of cancer.

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