Introduction
Cancer is the second leading cause of death in the world (Ferlay et al., 2015) and in recent years there have been many studies to carry out new methods for prevention, diagnosis and treatment of tumor cells and to decrease the side effects of treatment (Tao et al., 2015). In many of these methods a trace of nanotechnology can be found using different type of nanoparticles. In general, nanoparticles have dimensions between 1-100 nm2. Metal nanoparticles are at the center of attention because of their unique physical and chemical properties (Tao et al., 2015). Due to the remarkable optical, electrical and conductive properties of gold nanostructures, they have been extensively studied in a variety of applications (Fryer et
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When nanorods are concentrated around the diseased cells, they can be subjected to a continuous wave NIR laser in order to generate heat for photo thermal cancer therapy (Fourkal et al., 2009). Gold nanostructures can also be used as drug delivery vectors where they can concurrently assist to destroy cancer cells (therapy) using pulsed lasers (Mohseni et al., 2015; Lukianova-Hleb et al., 2010).
Hyperthermia as an adjuvant in cancer treatment has been developed in the last forty years. Different behavior of tumors and normal tissues against the heat applied depends on the vascular system. Temperature range of 41- 42°C should be lethal to tumor cells, whereas normal cells are not harmed. In fact, the difference of hyperthermia therapeutic effects between normal tissue and malignant mainly depends on the structure of these vascular networks and differences in the structure influences the behavior of the various tumors and tumor response to hyperthermia (Li et al., 2015). Earlier research on the application of gold nanoparticles in imaging and non-invasive treatment of cancer with gold nanospheres deformed cylindrical nanotube in removing malignant tumors in the deeper parts of the skin condition that is observed in breast cancer using laser beams is performed(Sharma et al., 2015). On the other hand, secreted cytokines from T cells such as IFN- and interleukins have destruction effects on tumor cells. However, in normal conditions, immune cells
In addition, it was shown that macrophages can mediate the delivery of gold-shell NPs into multicellular human glioma spheroids 76. In the report, gold-shell NPs are composed of a silica core coated with a thin layer of gold which greatly absorbs near-infrared light to generate local heat around NPs. Gold nanoshells (AuNS) NPs were loaded in macrophages via phagocytosis, and it is interesting to observe no apparent toxicity of macrophages after their uptake of nanoparticles 77. When co-incubated with human glioma spheroids, nanoparticle-laden macrophages can migrate and filtrate in the tumor as usual 78. Furthermore, two-photon fluorescence microscopy of glioma spheroids showed that nanoparticle-laden macrophages can accumulate in necrotic sites. When irradiated with 810 nm laser light, the growth of glioma spheroid dramatically decreased compared with the control without of nanoparticle-loading. The efficacy of macrophage-AuNS-mediated photothermal therapy (PTT) on glioma spheroids was also tested, and the growth of spheroids was dramatically suppressed. The same group continued to examine the therapeutic efficacy of macrophage-mediated delivery of AuNS nanoparticles in rat glioma tumor model 79. C6 rat glioma cells were directly injected into brain to generate brain tumor, following the injection of macrophage-AuNS delivery system. After NIR laser irradiation, it was observed that the tissue irradiated by laser was damaged, suggesting the therapeutic effect of AuNS.
As one of the most prevalent causes of death globally, cancer has been a main focus for bioengineers. While it is understood that, to treat cancer, malignant tissue must be resected, many issues arise when these tumors are not removed thoroughly, when the tumors are not determined accurately, or when more time has passed for the cancer to spread to other parts of the body. Currently, there are various technologies and applications that are being researched such as the application of microfluidic devices (Han, Park and Kim). Many of these emerging technologies are important to continue studying and developing for numerous biomedical applications, including cancer diagnosis. While there are various technologies and applications that are currently being studied, many of these are still considered to be new and need further application, trials, and approval. In addition to
In conclusion, cancer fighting nanobots are leading into our future and leading into more new discoveries in the medical field. This new technology will not only help everyone's live but also will help the lives of cancer patients, in medical form. This invention may just be the solution to help save millions of lives in today's
The efficient delivery of drugs and energy to tumors faces several difficulties and obstacles that need to be overcome for effective cancer treatment. Nanoparticles administrated through intravenous injections accumulate at a tumor site due to the enhanced permeability and retention (EPR) effect, but only a small quantity of the injected particles can actually “reach the tumor” (Su et al, 2016). The majority of the nanoparticles interact with “cancer cells at the periphery of a tumor” which presents a “physiological barrier” that prevents most of the injected particles from reaching the tumor (Su et al, 2016). In addition to this barrier, there is also another significant obstacle, “cancer-associated fibroblasts”, which can also
In the year 2000, the National Institute of Health (NIH) started the National Nanotechnology Initiative (NNI) as a federal government program for facilitating and promoting the different nanoscience related research. In order to accomplish the target the NNI was launched as a broad program. The main aim behind of establishing the NNI was to coordinating and supporting the study, design, and exploration of nanomaterial. With extensive effort and support of NNI, the research related to health science was highly influenced and become revolutionized. Due to this impact the US government given the financial support to a good deal of research and development program and launched the interdisciplinary research. The new concept ‘Nanomedicine’ is also a result of merging the ‘Nanoscience and Nanotechnology’ discipline with ‘Medicine’. Similarly, the pharmaceutical scientist also adopted a terminology ‘Nanoscience’, and created the ‘Nanopharmaceuticals’ [1].
In addition to peptides, protein-based ligands such as Affibody proteins have been utilized for tumor targeting. Anti-epidermal growth factor receptor (EGFR) Affibody protein (e.g., Ac-Cys-ZEGFR:1907, amino acid sequence: Ac-CVDNKFNKEMWAAWEEIRNLPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPK-NH2) is used to target EGFR that is overexpressed in a wide variety of human tumors. Cheng and co-workers used anti-EGFR Affibody protein as tumor-targeting ligand on 64Cu–Au-IO nanoparticles (PET component: 64Cu, MRI component: iron oxide, specific for EGFR) surface.[63] In their work, A431 tumor cells were subcutaneously implanted in the right shoulders of nude mice; and 64Cu-NOTA-Au-IONP-Affibody nanoparticles were administered via tail vain injection. Rather low resolution PET image showed that these nanoparticles were taken by EGFR positive A431 (human epithelial carcinoma cell line) cells reaching 4.6% ID/g at 24 h after injection, significantly higher than that obtained from the blocking experiment (1.9% ID/g) indicating the specificity of the probe. This difference in % ID/g values corroborated with 44% drop in MRI signal intensity that was observed for the tumor. In this study, the use of an Affibody protein as ligand for EGFR-expressing tumor in small animals was demonstrated to be successful; however, the benefit of multimodality was not demonstrated. The unique chemistry of this dumbbell-shaped Au–IO nanoprobe could pave the way for targeted drug delivery into EGFR-expressing tumors
The most clinically effective treatments for cancer were ironically incredibly detrimental to the human body 's health. These included, chemotherapy and radiation. These two methods did in fact destroy the malignant cells yet also caused apoptosis in healthy cells damaging them beyond repair and thus causing a great detriment to the patients health. However, recently, due to the endeavours of nanotechnology, it has been discovered that carbon nanotubes can effectively carry anti cancer drugs destroying the malignant cancer cells without damaging the healthy cells, in other words, the
All statistical analysis in this proposal will be done in collaboration with the Ohio State University Comprehensive Cancer Center Biostatistics Shared Resource. All cell based studies in Aim 1 will be performed in triplicate. All results will be summarized using mean ± SEM, range and median for each continuous measurement and as proportions with confidence intervals for each dichotomous measurement. For in vivo studies proposed in Aim 2, 5 animals per arm will be utilized to validate in vivo impact of nanoparticle delivered drugs. Immunofluorescence analysis of resulting tumors will be compared for differences between the groups using ANOVA generating two-sided p-values, adjusting for the molecular subtype and accounting for repeated measures over time. For the 4 group comparison,
In the past, the applications of light, more specifically laser, in health and clinical applications have been focused on its destructive phototoxic effects. This effect is associated with high energy radiation, whereas low energy radiation has been found to induce a stimulating effect on the cells. The heat inducing laser tissue ablation effect used in surgery and the disinfectant-antimicrobial effect of light therapy are distinctly different from the beneficial healing response stimulated by photobiomodulation (PBM). The nonionizing and low power lasers used in PBM are in wavelengths of visible (660 nm), near-infrared (810 and 940 nm), and in some rare cases, mid-infrared (1040, 2940, 9400 or 10400 nm)1. In recent studies, due to
Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new DDS to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both anti-tumor drugs and siRNA against ABCG2 were successfully delivered into CD133+ cancer cells of laryngeal carcinoma by loaded MSNs. Down regulation of ABCG2 significantly enhanced the efficacy of apoptosis induction by chemotherapeutic drugs in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles also inhibited tumor growth in vivo in a laryngeal cancer mouse model.
This is exactly what Shen and co-workers [29] did in 2013. They found that the silica-coated GNRs had both a significant potential in both photothermal therapy and drug delivery to tumorigenic regions. Of all the shapes of Gold nanoparticles, GNRs present the most ideal Near Infrared absorption cross section [30] and the highest thermal transmission efficiency [31]. Mackey, M.A and co-workers [32] did research determining what the most effective size of GNRs are for use in thermal phototherapy. They did this by comparing the plasmonic properties and efficiency of GNRs as photothermal contrast agents for three different size GNRs. The three-different size GNRs used were 38x11nm, 28x8nm and 17x5nm. What the results of the study showed was that the 28x8nm GNRs were the most efficient in plasmonic photothermal heat generation. This probed further analysis using in vitro experiments. This experiment compared the same three size GNRs and their ablation of human oral squamous cell carcinoma. The 28x8nm GNR was the most effective size nanorod. This size GNR displayed the best compromise between the absorption of Near infrared radiation and the size of the electromagnetic field around it. This sized nanorod had an electromagnetic field that extended far enough from the particle surface to the target cells to allow for field coupling. Whereas the larger GNRs showed to scatter too much of the energy rather than absorb it and the smaller
Drug delivery is the method of transporting a pharmaceutical compound to safely achieve its desired therapeutic effect in the body by using approaches, formulations, technologies, and systems. Today these technologies are nanobiomaterials and the use of nanobiomaterials are unprecedentedly increasing in drug delivery thanks to their significant advances in the diagnosis and treatment of disease. The major goals of using nanomaterials are to reduce toxicity, increase biocompatibility, safety, and specific cell targeting. Otherwise, nanoparticle-based vehicles in drug delivery is an important technology because of their small-sizes, easy penetration through cells, increasing cellular uptake, and capacity to carry large amounts of drugs, thus
In the article “Aptamer-Conjugated Nanoparticles for Selective Collection and Detection of Cancer Cells”, the method of rapid collection and detection of cancer cells is explored in detail and with an explanation of the procedure and modifications done to improve the system of cancer research. Current methods for leukemia diagnosis apply combinations of bone marrow and peripheral blood cytochemical analyses. Peripheral analyses include, karyotyping, immunophenotyping by flow, cytometry/microarray, and amplification of malignant cell mutations by PCR. Immunophenotypic analyses of leukemia cells use antibody probes to exploit the variation of specific surface antigens in order to tell the difference between normal and malignant cells. The
Nanotechnology-based drug delivery systems are the use of capsules between 1nm and 100nm large to store medicine within them and protect the drugs until it reaches the affected area it must treat. This method allows smaller amounts of drugs to enter the body and prevent severe side effects by reacting with unaffected parts of the body. These nanocapsules travel in the bloodstream and release the drugs once in close proximity to the affected area. The main focus for this application is to treat cancer, where the capsules can either identify and attach to cancer cells or a magnet worn by the patient can trigger the capsule once it reaches a specific place in the body.
Antimicrobial nanomaterials are gaining a lot of interest due their different modes of action. There are several mechanisms behind antimicrobial activity of a nanoparticle, and they can vary from one nanoparticle to another. The study of the interaction between the nanoparticles and the microorganisms is complex, because it depends on environmental factors of the surrounding, like temperature or pH; and properties of the particle, including chemistry, size and shape. (Beyth, et al., 2015). Some materials, like silver or copper (metals), have already antibacterial mechanisms in their bulk form, while others, do not present properties in their natural form, but can present them at nanoscale (Webster & Seil, 2012).