Tumor heterogeneity favors tumor tissue to survive and resist drugs, leading to the failure of chemotherapeutic agents to induce a therapeutic response. In addition, the absorption mechanisms,... Show moreTumor heterogeneity favors tumor tissue to survive and resist drugs, leading to the failure of chemotherapeutic agents to induce a therapeutic response. In addition, the absorption mechanisms, metabolism and excretion of chemotherapeutic drugs, which are commonly used for cancer patients and the lack of specific targeting of these drugs can cause adverse effects on treated patients. Thus, the general objective of this thesis is to investigate the biological activity of targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a drug delivery system (DDS) for carvedilol (CVDL) or oxaliplatin (OXA), in vitro and in vivo, to treat colorectal cancer (CRC). DDSs were formulated to achieve this goal. In chapters 2, 3 and 4, our studies were discussed in detail on the formulations and characterizations of NPs as DDSs with ideal characteristics to increase the therapeutic range of drugs at the tumor site. As well as the biological evaluation of these DDS when its anti-inflammatory activity (Chapter 2) and its antitumor activity in vitro (Chapters 2, 3 and 4) and in vivo (Chapters 3 and 4). Taken together, all the DDSs studied in this thesis were able to improve the chemotherapeutic efficiency of the drugs studied in Chapters 2, 3 and 4. Show less
Fluorine-19 (F-19) magnetic resonance imaging (MRI) features one of the most investigated and innovative techniques for quantitative and unambiguous cell tracking, providing information for both... Show moreFluorine-19 (F-19) magnetic resonance imaging (MRI) features one of the most investigated and innovative techniques for quantitative and unambiguous cell tracking, providing information for both localization and number of cells. Because of the relative insensitivity of the MRI technique, a high number of magnetically equivalent fluorine atoms are required to gain detectable signals. However, an increased amount of F-19 nuclei induces low solubility in aqueous solutions, making fluorine-based probes not suitable for in vivo imaging applications. In this context, nanoparticle-based platforms play a crucial role, since nanoparticles may carry a high payload of F-19-based contrast agents into the relevant cells or tissues, increase the imaging agents biocompatibility, and provide a highly versatile platform. In this review, we present an overview of the F-19-based nanoprobes for sensitive F-19-MRI, focusing on the main nanotechnologies employed to date, such as fluorine and theranostic nanovectors, including their design and applications. Show less
In this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting... Show moreIn this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting nanoparticles loaded with various immunologically active molecules (immunomodulatory nanoparticles) that can modulate the immune system to attack cancer cells more efficiently. The effectiveness of this immunomodulatory nanoparticles have been studied on different mouse cancer models and investigated as a single treatment or in combination with other known therapies, such as chemotherapy, therapeutic cancer vaccination, or photodynamic therapy. Show less
In cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting,... Show moreIn cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting, thereby potentially enhancing therapeutic effect and reducing undesired off-target effects. However, a large number of administrated nanocarriers often fail to reach the tumor area. In the present study, we show that photodynamic therapy (PDT) enhances the tumor accumulation of systemically administered lipid-PEG layer coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Intravital microscopy and histological analysis of the tumor area reveal that the tumor vasculature was disrupted after PDT, disturbing blood flow and coinciding with entrapment of nanocarriers in the tumor area. We observed that the nanoparticles accumulating after treatment do not confine to specific locations within the tumor, but rather localize to various cells present throughout the tumor area. Finally, we show by flow cytometry that NP accumulation occurred mostly in immune cells of the myeloid lineage present in the tumor microenvironment (TME) as well as in tumor cells, albeit to a lower extent. These data expose opportunities for combination treatments of clinical PDT with NP-based immunotherapy to modulate the TME and improve antitumor immune responses. Show less