Nanomedicine is based on drug delivery using nanomaterials as nanocarriers. More recently, nanomaterials have been developed to play a pivotal therapeutic role by their own. Many research programmes dealt with in vitro and in vivo applications of nanoparticles in radiation therapy. Given that radiation therapy is not a selective anti-tumour treatment, the main challenge for radiation oncologists, medical physicists and radiobiologists is to increase its therapeutic efficacy without increasing damages dealt to the surrounding healthy tissues. Hence, the goal of combining nanoparticles with radiation therapy is to increase the differential effect between healthy and tumour tissues. How nanoparticles work in drug delivery system and how exactly nanoparticles able to improve the radiation therapy in cancer. Please provide at least two examples of nanoparticles and their application in radiation therapy. Usage of schematic figures, graphs, tables etc are recommended.?????? (20 marks)??Nanomedicine is the application of the nanotechnologies in healthcare setting like the usage of nanoparticles in improving the behaviour of the drug and reducing the side effects of the drugs. Nowadays, the nanomedicines are applied to improve the treatments and lives of patients that suffer for ovarian and breast cancer, kidney disease, chronic pain, asthma and fungal infections (The British Society for Nanomedicine, n.d.). The nanotechnologies have been developed to improve the disease diagnosis, treatment and prevention as the nanoparticles can mimic and alter the biological process. Nanoparticles, solid and small particles with size range 10 to 100 nanometers (nm) work in drug delivery system, while nanocapsules are vesicular system of a drug that is confined to a cavity surrounded by a polymer membrane and nanospeheres are the matrix system for the drug to disperse physically and uniformly. Nanoparticle is a combination of nano, from the Greek “nanos” (or Latin “nanus”), meaning “Dwarf”, and the word “Science”. Nowadays, nanoparticles have been applied in few medical applications as the particles have great potential benefits for patients as well as medical provider. (Phys.org., 2014). According to Singh, R. and Lillard, J. (2009), usually the drug of interest is dissolved, adsorbed, entrapped, encapsulated or attached into or onto a nanomatrix. To have characteristics of the best delivery or encapsulation of the therapeutic agent, nanoparticles, nanospheres or nanocapsules can be constructed to possess different properties which are depending on their method of preparation. ?One of the uses of nanoparticles is to treat cancer cells. Cancer is a class of diseases characterized as uncontrolled cell growth and it harms the body when the damaged cells divide uncontrollably to form lumps or masses of tissue called tumours (Chakraborty, 2017). For those who diagnosed with cancer, there are few treatments which depend on the stage of their cancer including surgery, radiation therapy, hormone therapy, chemotherapy and biological therapy. The typical side effects of current treatments are painful, frequent urination, hot flashes, lost of bone mass and the side effects chemotherapy are hair loss, nausea, vomiting, weakness and fatigue. However, these therapies will cause the normal cells also being killed. Thus, the use of nanoparticles in treating cancer is more preferable as it only attack the cancer cells instead of healthy cells. Nanoparticles help to reduce the side effects of cancer drugs as the nanoparticles easier to be recognized bytumours than normal tissues and they also enhance the absorption of drugs into cancer cells. According to Jayanth Panyam, a professor in the Department of Pharmaceutics at the University of Minnesota, the method on how nanoparticles work has been shown in a lab work with rats and mice. He proved the effectiveness of the technique by injecting nanoparticles into tumours in mice. When he subsequently put the mice inside of a small magnetic coil, he successfully killed tumour cells(Abrams, 2015).?Nanoparticles for anti-cancer drug delivery had reached the first clinical trial in the mid-1980s, and the first nanoparticle which is liposomal with encapsulated doxorubicin had entered the pharmaceutical market in 1995. Then, numerous new nanoparticles for cancer drug delivery have been approved and are currently under development due to their advantages. Some advantages of nanoparticles are enhancing solubility of hydrophobic drugs, prolonging circulation time, minimizing nonspecific uptake, preventing undesirable side effects, improving intracellular penetration, and allowing for specific cancer targeting (Nguyen, 2011). The use of nanotechnology in cancer therapeutics can improve the pharmacokinetics and reduce the systemic toxicities of chemotherapies through the selective targeting and delivery of these anticancer drugs to tumour tissues. Due to nanosized carriers, they can increase the delivered drug’s overall therapeutic index through nanoformulations in with chemotherapeutics, either encapsulated or conjugated to the surfaces of nanoparticles. The particles size has play important roles in the delivery of nanotechnology-based therapeutics to tumour tissues. While the selectivity of the nanotherapeutic is depends on the passive targeting of tumours through the enhanced permeability and retention (EPR) effect. This phenomenon relies on defects specific to tumour microenvironment such as defects in lymphatic drainage, along with increased tumour vasculature permeability, to allow nanoparticles to accumulate in the tumour microenvironment. In addition, the site of drug release can be controlled by ultrasound, pH, heat, or by material composition(National Cancer Institute, 2017).?One of the examples of nanoparticles for cancer treatment is gold nanoparticles which coated with the cancer drug and used to target and kill the cancer cells. Researchers found that the gold nanoparticles are attracted to disease regions inside the body such as cancer cells which enables the gold nanoparticles being used in targeted drug delivery. Gold nanoparticles(GNPs) have high atomic mass which can absorb significantly more radiation than soft tissue cells, thus making them ideal for boosting the radiation dose in the tumours (Phys.org., 2014). Due to its small size, high surface area ratio and being chemically inert gold acts as an active vehicle which binds specifically to the tumour cell. The main advantage of GNPs is that they minimize the toxicity of the anti cancer drugs. Gold nanoparticles are composed of gold core with monolayer on the outside, which is non toxic and relatively inert so it is safe for the human body. The monolayer is a part of the nanoparticles that contain the drug and other molecules for the cancer treatment. These nanoparticles have unique physical and chemical properties which is suitable to be used in drug delivery. The surface of the gold nanoparticles can be modified which allowing it to be coated with small polymers and other therapeutic agents such as the cancer treating drugs. This condition enables the patient’s DNA to be transcribed onto nanoparticles, thus the body does not treat the nanoparticles as an invader or foreign and reject it. In addition, the applications of gold nanoparticles are for photodynamic therapy, therapeutic agent delivery and diagnostics which to detect biomarkers in diagnose the cancers, heart disease and infection agents. Gold nanoparticles also can be applied by acting as catalysts in number of chemical reactions (Sigma-Aldrich, n.d.). Image 1: The image shows gold nanoparticle is a charge particle which experience repulsion thus prevents them from aggregation. This characteristic enhances the gold nanoparticle to work inside human body by targeting the cancer cells. ?In term of size, nanoparticles have diameter less than 170 nanometers which can effectively fit through and diffuse inside cells and capillaries. In addition, these nanoparticles are charged particles which experienced repulsion to prevent them from aggregating. The charged nanoparticles also help them to interact with cells better. In delivery the chemotherapeutic drugs, the gold nanoparticles act as vectors and target the cancer cells. Docetaxel and Doxorubicin are the examples of the cancer treating drugs that being used with nanoparticles which act as toxoid. The vectors accumulate within the tumour and the vectors ensemble dissociates to release the toxoid. The toxoid causes apoptosis which is death of the cancer cells. When the gold nanoparticles is injected into the cancer patient, it will spread into the blood stream. Then, the nanoparticles selectively infiltrate the cancerous cells. Next, a low energy-short laser pulses will be fired onto the nanoparticles, the particles will heat up and vaporize the water inside the cancer cells and creates tiny bubbles inside the cells. Then, the tiny bubbles quickly expand and burst thus, rip the cancer cells. This new therapy is 17 times more efficient than conventional therapy as it kills cancer cells without harming the normal cells. Besides, it can destroy the cancer cells that cannot be removed by surgical including aggressive cancer cells that resistant to radiation and chemotherapy(National Cancer Institute, 2017).Image 2: The image shows how gold nanoparticles work in killing cancer cells. At first, the cancer is diagnosed, then gold nanopartciles injected into human body to target the tumour. When laser isexposed to the patient, nanoparticles at the cancer cells are targeted. The nanoparticles work on the cancer cells thus recovery will occur. ?According to Provenzale, J. and Silva, G. (2009), in research studies, it stated that gold nanoparticles produce covalent bond with the cytotoxic drug and do not react with any other molecule. Targeted cell therapy is achieved in GNP drug delivery system and special interaction between light matters at right wavelength. Thus, gold nanoparticle has become a precise cancer cell killer. Infra red light is used to oscillate the gold nanoparticles attached with the cancer cell and the energy formed due to oscillation. The heat and temperature cause increasing in the killing of the cancer cells. However, radiation effects enhanced by the nanoparticles are depend on cellular uptake of nanoparticles which is smaller nanoparticles could penetrate the cell nucleus and interact with DNA molecules, nanoparticle size, concentration and also charge. ?The other example of nanoparticles use in cancertherapy is dendrimers; highly branched, star-shaped macromolecules with nanometer-scale dimensions. According to history in the early 1980s and in 2008, the first dendrimers were synthesized by Tomalia and co-workers at Dow Chemical there were over 10 000 scientific reports and 1000 patents dealing with dendritic structures (Tabirsir, 2011). There are three majorcomponents of dendrimers which are a central core, an interior dendritic structure (the branches), and an exterior surface with functional surface groups. The variety of combination of these components yields give different shapes and sizes with shielded interior cores of the dendrimers. Nowadays, dendrimers have been explored for the encapsulation of hydrophobic compounds and for the delivery of anticancer drugs. There are three methods for using dendrimers in drug delivery. First, dendrimer prodrugs will be formed by attaching of the drug to the periphery of the dendrimer to form dendrimer prodrugs via covalently. Second, the drug is coordinated to the outer functional groups viaionic interactions and third, the dendrimer acts as a unimolecular micelle by encapsulating a pharmaceutical through the formation of a dendrimer-drug supramolecular assembly.Image 3: The structure and characteristic of dendrimer as nanoparticle?There are few requirements for dendrimer-based,cancer-targeted drug delivery. First, dendrimers that have multiple surface functional groups can be directed to cancer cells by tumor-targeting entities that include folate or antibodies specific for tumor-associated antigens (TAAs). The next step is to be intake into the cell, which in the case of folate targeting occurs by membrane receptor mediated, endocytosis. Then, once inside the cell, the drug generally must be released from the dendrimer. Dendrimers offer many advantages over viruses as vehicles of genes. Dendrimers are less toxic, ease of production and ability to transfer long genes. For example, Polypropyleneimine dendrimer nanoparticles which is capable for tumour transfection; the process of introducing nucleic acids into cells by non viral methods in tumour bearing mice. Once inside the cell gene, the particle recognises the cancer cells and kills them. However, in human trial is not being done yet (Vijitha, 2014). ?Dendrimers as drug delivery carriers have great interest due to their highly controllable structure and size, and the terminal functional groups of dendrimers show higher chemical reactivity compared with other polymers. Besides, the functional groups of dendrimers have been conjugated to various biologically active molecules. A research of Polyamidoamine (PAMAM)dendrimers have been extensively investigated for oral drug delivery as they are a family of water-soluble polymers characterized by unique tree-like branching architecture and a compact spherical shape in solution. PAMAM dendrimers act as a drug carrier as consist oflarge number of arms and surface amine groups which is important in utilization to immobilize drugs, enzymes, antibodies, or other bioactive agents. On the other hand, there are few applications of dendrimers which are being used for cancer imaging, photodynamic therapy, DNA-dendrimer conjugate and gene therapy (Vijitha, 2014).?The other example of the nanoparticles for treating cancer cells is Abraxane nanoparticles; nanoparticle albumin-bound paclitaxel (Abraxane) which has been approved by FDA for treating in patients with metastatic breast cancer and non-small-cell lung carcinoma. By history, nanoparticle albumin bound paclitaxel (nab-paclitaxel) is the first nanotechnology-based drug being used in cancer treatment. According to Zhao, M., Lei, C., Yang, Y., Bu, X., Ma, H., Gong, H., Liu, J., Fang, X., Hu, Z. and Fang, Q. (2015), drug delivery via nanoparticle-based carriers has shown promising pharmacological improvements in cancer therapy. Abraxane is a nanoparticle with 130 nm size, albumin-bound particle form of paclitaxel (PTX), which is a member of the taxane family and an important agent in cancer chemotherapy. PTX acts by binding to microtubules and interfering with the mitotic process. Abraxane is less toxic and improves the drug effect in tumour by enhancing the permeability and retention effect. ?In conclusion, there are potential risks and challenges even targeted nanoparticles have emerged as one strategy to overcome the lack of specificity of conventional chemotherapy. For instance, some cancer cell types would develop drug resistance over the drug treatment course, thus cause targeted nanoparticles to be ineffective. Therefore, combined therapies (chemotherapeutics and gene therapeutics) can be used to target nanoparticles for delivering. This might be effectively delivered and specifically targeted to cancer cells and tissues to overcome this drug resistance and to stop the tumor growth. Development of multifunctional targated nanoparticles also a strategy to overcome the drug resistance. Similar to other new technologies, targeted nanoparticles for cancer therapy also face many challenges. One challenge is the nanoparticlesmight change the stability, solubility, and pharmacokinetic properties of the carried drugs. Besides, the shelf life, aggregation, leakage, and toxicity of materials used to make nanoparticles are other limitations for their use (Nguyen, 2011).?Besides developing new materials and selecting appropriate materials for each specific treatment, other factors need to be optimally selected in order to design better targeted nanoparticles. These factors include the particles size, shape, sedimentation, drug encapsulation efficacy, desired drug release profiles, distribution in the body, circulation, and cost. For instance, as the naoparticles size have small size, it has been known that the clearance rate of the nanoparticles will be high and most of them might metabolize in liver ad spleen, thus resulting the use of targeted nanoparticles impractical and ineffective. On the other hand, larger nanoparticles might be too big to go through small capillaries for drug delivery. Thus selecting the right materials and particle size is another important aspect in targeted nanoparticles for cancer therapy. Until today, the only a few of them are in clinical use including Abraxane®, Doxil®, and Myocet™ that are approved by FDA as there is not enough knowledge about the distribution and specific target of the nanoparticles after oral admiistration or injection. For example, most studies have not examined the targeting efficiency of nanoparticles real time in vivo, thus precise bio-distribution and subsequently therapeutic effects are not well-known. Therefore, it becomes the limitation for detecting cancer in the body and monitoring treatment effects on these cells in order to improve the development of the efficient targeted nanopartciles(Nguyen, 2011).?Despite of that, nanotechnology by using nanoparticles have provided an effective platform for a better and more specific delivery of cancer therapeuticswith their own risks and benefits of targeted nanoparticles for cancer therapy and multifunctional targeted nanoparticles can be designed. These targeted nanoparticles would be able to detect cancer cells, visualize the tumour location in the body, deliver drug to cancer cells and kill cancer cells while harmless thenormal cells with minimal side effects and monitor treatment effects in real time. Last but not least, the role of nanoparticles in drug delivery is keep growing until today and it is believes that nanopartciles can be future nuclear medicine (Nguyen, 2011).