Resumen de Optical methods and nano/microsystems for cancer diagnosis and therapy
Cancer disease represents one of the most widespread public health problem still to be solved. As a genetic disease, the heterogeneous nature makes challenge to find out a general solution for its prognosis, diagnosis and treatment. Consequently, efforts have focused during decades on studying and understanding the genetics and further molecular basis behind the disease. Mainly, cancer is product of a deregulated cell division resulting in a solid tumor formation than can become malignant and metastasize to surrounding tissues, travelling within the bloodstream. Lots of cancerous material can be released to the blood in form of nucleic acids, proteins or cells, and its detection and analysis can provide relevant information of the pathogenesis. Molecular identification of those materials not only can advise about the progression of cancer, but also can instruct of subsequent treatment for its eradication.
Several specific and high-sensitivity fluorescent techniques and other optical methods, such as surface-enhanced Raman scattering (SERS), are commonly used, as in immunohistochemistry, for classification of cancer and molecular evaluation, with slices from solid tumor biopsies. Recently, liquid biopsies have gained relevance in clinical oncology, since they represent a potential alternative to invasive biopsies due to their easy manner of sampling collection.
In this stage, the main objectives of this experimental work are: (i) to develop new optical methods for detection of cancerous material in liquid biopsies and (ii) to build up a platform for cancer targeting and therapy.
To successfully accomplish these purposes, two different strategies will be approached for cancer diagnosis: one method based on the use of a fluorescent label to highlight entire cancer cells (CTCs) front normal cells in human blood and its application in lung cancer diagnosis, and a second method, based on a SERS platform for detection and quantification of an oncoprotein c-MYC in breast cancer. For cancer therapy, a platform based in a hybrid material is engineered to specifically target and eliminate HER-2 breast cancer cells in vitro.
Accordingly, this dissertation comprises five different chapters:
In Chapter 1, it will be described the molecular basis of cancer, exploring from genetics to aberrant behavior of cancer cells and the metastatic process to secondary sites. The second part of the chapter will focus on explaining physical concepts behind the optical techniques used in biomedical research.
The first method developed for cancer diagnosis will be shown in Chapter 2. Basically, it consists in the exploitation of cancer behavior to acquire larger amounts of sugars to support metabolic requirements. Using a fluorescent glucose analogue 2-NBDG it will be describe a methodology to identify cancer cells within human blood, under optimized conditions.
After its description and demonstration, the developed method in previous chapter will be implemented in Chapter 3 for the detection and quantification of CTCs in patients with human lung cancer at different stages of the disease. The results of the method will be contrasted with conventional clinical oncology techniques.
Chapter 4 will focused on the explanation of a second developed method for cancer diagnosis, as well. This is based on the construction of a nano/microsystem composed by silica microbeads decorated with silver plasmonic nanoparticles. By holding a SERS reporter the sensing platform is able to induce a quantitative optical response when detecting c-MYC oncoprotein from both breast cancer cell lines and cancer patient blood.
To end, an immunotherapeutic agent will be described in Chapter 5 for cancer targeting approaches. Silicon microparticles will serve here as essence of the system, carrying antibodies to target specific HER-2 positive breast cancer cells and covered with a protection shell that triggers its toxicological effect upon internalization by cancer cells in vitro.
In global, this work has provided two new optical liquid biopsy methods: one based on a universal metabolic pathway proven in specific human lung cancer samples and another using a protein recognition nano/microsystem applied to breast cancer; and an engineered system, as a therapeutic agent for specific breast cancer, evidencing the potential of biophotonics and nanomedicine in the field of cancer research.
