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A novel approach for tumoral targeted phototherapy: focusing light through scattering

This proposal outlines a R&D programme aiming the study of new methodologies for concentrate light inside turbid biological media, one of the last frontiers in laser biomedical applications. The target: phototherapy by thermal activation and destruction of cancer cells.
The backbone of the proposed research is the development of a phase shaping method based on an iterative algorithm to create wavefronts inverting the diffusion of light. This algorithm will be developed, being the interrogation and phase partitioning strategies critical points to be considered when analysing its performance. Two main types of laser beams will be considered in the study (Gaussian and quasi-Bessel beams) and the potential of low coherence beams to improve the method will be analysed. The core scientific objectives to be pursued are:
– To produce and characterize multifunctional nanoparticles which phototherapeutic potential can be improved by their in-depth activation.
– To develop a new methodology based in phase shaping to concentrate light inside turbid biological media.
– To develop a simulator capable of predict the focusing capability of the methodology for a determined set of parameters.
– To demonstrate the technique by its experimental application under well controlled conditions.
– To demonstrate the technique in vitro and in vivo.
– To evaluate the potential, limitations and future developments of the technique.
Although light has long being used in biomedicine, scattering always limited its application. Superficial (tenths of micron for human epidermis) phototherapy is already a well established application, requiring intrusive methods to deliver light when the target is deeper inside the body. The latter solution removes the major advantage in using light: its non-intrusive potential. This motivates researchers to develop methods to concentrate light inside biological highly scattering media. However, only a few years ago phase shaping approaches have started to be developed for focusing light through turbid media, although not exactly directed to biological media. The idea: to use a phase modulator to produce wavefronts inverting the diffusion of light based on a close-loop approach. In biophysics, the research in this area as been mainly focused in increasing the depth light can propagate, with direct application in imaging techniques like microscopy and tomography. In these fields, scattered light is collected and its analysis allows imaging. In order to increase the observable path, several strategies have been envisaged. A recent one has been developed for optical coherence tomography by using quasi-Bessel beams. These beams have shown the capability of self-reconstruct along the turbid path thus allowing collect scattering at longer paths.
In this work we propose to further develop the phase-shaping principle with a dedicated approach to biomedical applications, in general, and photoactivation in particular. The preconditioning of the incident beam to a quasi-Bessel beam will increase the propagation of the beam, although scattered. Then, the developed phase shaping technique will act, concentrating the light where necessary. The use of these beams is expected to remove computational load of the iterative process and allow a better and faster convergence to a solution. The technique will be developed considering the parameters regarding a set of photosensitize substances identified as potentially relevant for the study.
A simulator will allow overcoming a limitation of the technique: its requirement of feedback information on the intensity distribution in the plane where light concentration is required. By using an optical design and scientific programming software, and by proper experimental validation, it will allow predicting the method’s performance in an open loop process (as in real applications).
A numerical model will be developed to predict the effects of a concentrated light beam on the considered substances and surrounding media.
The institutions proposing this candidature have a combined set of experiences that potentiate the development of this research. From FCUL, IBEB, CFA and LOLS joint forces will use they expertise in biomedical and light-matter interaction. FCTUNL has expertise in the application of optical techniques in the biomedical field, in particular but not exclusively in the area of ophthalmology, aiming the development of new techniques and methodologies for medical application. INL (BioPhotonics Group) will contribute with its expertise in the fields of phototherapy of cancer cells; photochemistry and biophotonics; synthesis, characterization and biofunctionalization of nanoparticles and bioimaging. COFAC, with its BioSciences Center (CBIOS), and INL will contribute with their expertise in the fields of multifunctional nanoparticles development and drug delivery for tumor therapy. In vivo tests will be performed at the Faculty of Pharmacy of the Univ. of Coimbra
Principal Investigator: João Miguel Pinto Coelho (IBEB and LOLS)