Abstract
Cancer and atherosclerosis are the main causes of mortality and morbidity in the world. One of the strategies to treat cancer, based on nano technology, is the magneto hyperthermia, where the magnetic nanoparticles, incorporated in the cancer cells, are subjected to an external radiofrequency and that combined with other approaches such as immunotherapy, enhancing the therapeutic effect in the treatment from cancer. Another, is the use of nanoemulsions (NE), that internalize in cancer cells potent drugs, with low side effects. The possibility of merge both strategies in a single particle, has not been achieved till now. Our idea is to incorporate small magnetic nanoparticles and anticancer drugs in a single nanoparticle emulsion. We propose to build a facility to produce the chip-on-demand microfluidic devices, for the purposes of this research. In the following, we describe more specific lines of research, employing the complex nanoparticles and the Lab-on-chip (LOC) devices. We propose a new approach for the treatment of metastatic melanoma by applying cholesterol NE with Paclitaxel and immunotherapy based on tumor infiltrating lymphocytes. The evaluation of immunotherapy with T lymphocytes (TILs) obtained from metastatic melanomas can be performed using microfluidic devices (organ-on-a-chip, OOC), where the chip has the ability to mimic the tumor environment in a 3D culture with the presence of extracellular matrix, vessels, among other components. Using the OOC modality, it is possible to mimic different organs or a complete system, allowing to simulate the metastatic process beyond the tumor. The monitoring of administered TILs can be performed through the internalization of nanoparticles in lymphocytes. These nanoparticles can be functionalized with the addition of fluorescent molecules or radioisotopes, enabling tracking by molecular imaging techniques. We aim: in silico - simulate the drug intake with the objective of evaluating the efficacy and safety of the molecules in the therapeutic process, as well as the development of microfluidic devices with the purpose of finding the best characteristics for manufacturing these devices; in vitro and in vivo - evaluate the assessment of LDE-Paclitaxel (LDEP) toxicity, characterize the metastatic melanoma tumor cells, analyze the interaction between LDEP and the tumor cells, and the therapeutic. We aim to evaluate the therapy for glioblastoma multiforme using cholesterol-rich NE coupled to Paclitaxel: in silico, in vitro, in vivo and TOC study. We propose to develop a model of Glioblastoma-on-a-chip based on a microfluidic device to evaluate the therapeutic efficacy achieved with the use of LDEP and thus be able to become closer to translational research of applicability to the patient, using platforms such as in silico, in vitro, in vivo and tumor-on-a-chip. Besides the incorporation of the drug in the LDE, the incorporation of magnetic nanoparticles allows the employment of hyperthermia in addition to the chemotherapy. In the case of the atherosclerosis, we aim to investigate the functionality of high-density lipoprotein (HDL) in individuals of the SHIP-Brazil cohort. We search for correlations between the characteristics of the HDL with the development of the atherosclerosis. We will investigate possible interventions in the plaque with drugs and hyperthermia, allowed an eventual incorporation of the NE on it. After the synthesis, the process that involves the incorporation of the active matter to the NE and its characterization are accomplished, the next steps will be the in vitro essays in microfluidics devices to test toxicity, efficiency of incorporation in cells and effectiveness of the therapy. In the following, in vivo essays will be performed. The relation between breast cancer and dyslipidemia will be investigated. The LOC platforms will be used to investigate the periodontitis, which was shown to be related to the development of the atherosclerosis. (AU)
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