Biophotonics

Our focus can be distributed on four main fronts: Diagnostics in general with optical techniques, cancer treatment, microbiological control and photobiostimulation. In the diagnostics part, we use concepts of optical fluorescence both resolved in time and in frequency, as well as recognition of fluorescent or far-field images. For the treatment of cancer, our main work element is the photodynamic action, where light excites target molecules introduced in the biological system and promotes the formation of reactive oxygen species and/or free radicals that results in oxidative reactions, ending with the destruction of cancer cells. Still in the treatment of cancer, we use ionizing radiation combined with photodynamic action as well. In microbiological control, the physical elements of use are photodynamic action and the use of ionizing radiation in the UVC region of the spectrum. Microbiological control today occupies a large fraction of the research and treatments, developing fundamentals, proof of principles and clinical applications in a wide variety of situations. Finally, in the photo-biostimulation part, we use natural responses from biological molecules, so that with the use of light, we can interfere in cell metabolism for repairing effects. It is important to say that on all fronts we work, we analyze from the basic aspects how we carry out proofs of principles. In many cases, we reach clinical applications, where our Clinical Trials Center, at the Hospital Amaral Carvalho de Jaú, carries out the studies with all the necessary rigor. On the diagnostic side, the main focus has been on agriculture and the optical dection of skin cancer. Together with Embrapa, LIBS - Light Induced Brakdown Spectrsocpoy techniques have provided the understanding and introduction of several new ways of evaluating the nitrogen content, wet matter, inorganic matter and other soil components. The technique has been one of the most useful tools in so-called precision farming. Fluorescent techniques have also allowed the determination of the water stress of plants, even by remote viewing. In addition to these techniques, our OCT laboratory - Octical Coherent Tomography, has allowed a great advance in the area of skin age characterization and the determination of aging patterns. With age, the distribution of the caliber of peripheral blood vessels changes and this can be measured by OCT, allowing the assessment of skin age, as well as the relationship of these changes with the occurrence of skin cancer, among others. Basic aspects of this research seek to understand the reason why the vessels become thinner on average during aging, allowing only the passage of blood plasma as a source of tissue nutrients. The decrease of read cells circulation in the peripheral parts, causing a decrease in peripheral oxygenation and leading to variations in the skin. The first work in this line are in preparation and will be a new front and a new way to visualize the aging process of the skin. Microbiological control has been growing in importance and our studies have reached stages of development that are already reaching clinical applications. Seeking to control fungi, bacteria and viruses using photodynamic action and also chemical breaks with UVC radiation, a large number of experiments and well-structured projects are being carried out in several laboratories. When applying the photodynamic action in microbiological control, one of the most important parameters to be determined is the microbial elimination curve versus the applied light dose, for a given concentration of photosensitizer. Our work has demonstrated and created models that allow comparison of different types of photosensitizers and also for different microorganisms. An excellent work published in Applied Physical Review, demonstrated the use of these techniques to fight viral infections. A work to generate fundamental knowledge in the field was developed in this period of activity. We have demonstrated that bacteria resistant to antibiotics, when exposed to a moderate photodynamic action, lose this resistance. This is a fact of great relevance for combating resistant bacteria and fungi. This was a work of great prominence in the period. Within this theme, the combined use of antibiotic with photodynamic action reveled the presence of competitive effects, so that the combined use does not necessarily lead to advantages. This is a theme that should continuos as part of our plan and must have many other consequences. All microorganisms causing infection shown in an illustrative figure in this report have been the focus of our studies. Among the applications developed for the use of microbiological control are techniques for the decontamination of organs for transplants, a fact that has been happening for several years, with a success and great impact. In addition to this application, our studies for decontamination of endotracheal tubes have evolved rapidly. Through the functionalization of the tubes, and the use of an optical fiber attached to the tube, the formation of bacterial colonies and the evolution to pneumonia is remarkably avoided. Our students and researchers have evaluated the efficiency of this process, including the construction of an unprecedented system of artificial tracheas for testing and studies. Still, within the applications of photodynamic action as an element of infection control, the work of great prominence has been the control of pulmonary infection through the inhalation of a special molecule that associates bacteria, followed by extracorporeal lighting that promotes elimination of bacterial colonies. Within this study, we have already passed through small animals and are now carrying out experiments with pigs. Some challenges are presently being investigated and once resolved we shall be able to start clinical trials. This should be a great contribution from our center to the world regarding a huge problem: bacterial resistance to antibiotics and pneumonia. For applications in the environment, we take photodynamic action to combat the vector of the aedes aegypti mosquito, which causes several diseases. The results of scientific studies were very good, showing that molecules based on curcuminoids are ingested by larvae, which exposed to sunlight can undergo oxidation and be eliminated. Work towards larval control has now evolved to become the subject of a technological innovation with companies. Similarly, the control of biological contaminants in food has also been an important part of the list of studies being carried out by our Center for the finishing period of activities. Cancer and photodynamic treatment are the theme of our pioneering efforts in the country. With the advancement of our understanding of these treatments, we have reached an incredible 95% efficiency of the photodynamic action in the treatment and elimination of skin tumors, non-melanoma from small areas. The so-called single visit treatment, in which patients can get free of the disease with a single visit to the medical center, may have big impact in the Brazilian society and in the world. This is followed by more than 15 articles in animal models and an equivalent number in clinical trials. More recently, we have developed soluble microneedles to increase drug delivery to superficial tumors, overcoming the problem of incubation time required for penetration of molecules through topical cream. With this, we improve the uniformity of drug distribution in the tumor and increase its penetrability. With this we hope to reach about 97% efficiency in the treatment of skin lesions, and with this to receive approval for use in the SUS network, with great savings and numerous advantages over surgery. Using photobiomodulation, we developed techniques that combine photostimulation with negative pressure or ultrasound, generating equipment and protocols that have allowed the treatment of chronic diseases such as Parkinson's, alleviating the symptoms of muscle discomfort as well as fibromyalgia, with the promotion of regenerative and anti-inflammatory stimulation in the essential points that allow to increase the pain tolerance threshold. These techniques form a great success and have reached the market through the various technological innovation partnerships that we maintain at the Center. The Biophotonics part is the most numerous in our center, and every day we have received proposals for partnerships with various institutions in the state of São Paulo and Brazil. It is undoubtedly one of the fundamental elements of our relevance, which would not be possible without the part of basic research fueled by atomic physics.