A new paradigm for photodynamic therapy: coherent control

Photodynamic therapy (PDT) is a treatment based on the interaction of light, photosensitizing agents and tissue oxygen. The light delivery in PDT is usually optimized by controlling the intensity, the spectrum, and/or the dosage of excitation light. In this paper, we introduce a novel method that aims to improve the efficiency of PDT by controlling the phase of the excitation light, an important and so far neglected parameter. This coherent control approach utilizes the coherence properties of light-matter interaction and aims to manipulate the quantum interferences between various available reaction pathways. In general, an outcome of a photochemical reaction can be optimized by enhancing the desired reaction pathways and suppressing other unwanted pathways. Such optimizations can be done by appropriate tailoring of the electric field profile of a broadband coherent excitation light, i.e. ultrafast laser pulse. Here, we used a femtosecond laser source with adaptive pulse shaping together with a molecular feedback in a learning loop to search for and synthesize such 'smart' laser pulses. Our control objective is to enhance the triplet yield of a model photosensitizer zinc phthalocyanine (ZnPc), which then leads to enhancement of the overall PDT process. We use two coherent control schemes where we optimize the ratio between the excited singlet state (S) and triplet state (T) ZnPc molecules both ways (S/T and T/S). We demonstrate a control of 15% over the triplet yield between the found best and the worst pulse shapes. Our preliminary results show that phase shaping can indeed be used in manipulating photosensitizer photophysics and correspondingly the yield of singlet oxygen.