Insights into the Excited State Dynamics of Donor-Acceptor Organic Photosensitizer for Precise Deep-Brain Two-Photon Photodynamic Therapy

Organic photosensitizer with both large two-photon absorption (sigma) and efficient intersystem crossing (ISC) offers incomparable advantages in precise two-photon photodynamic therapy. However, the current design strategy cannot achieve efficient ISC without compromising sigma. Here, very efficient ISC and ultrahigh sigma in organic photosensitizer (PFBT) for precise cerebrovascular two-photon photodynamic therapy is simultaneously achieved. A hybridized local and charge-transfer (1HLCT) excited state in PFBT, formed by incorporating benzothiadiazole into a typical polyfluorene (PF), is the key to initiating efficient ISC while bringing substantial sigma enhancement (25 000 GM vs 10 000 GM) compared to PF. Mechanism studies identify that 1HLCT produces large spin-orbit coupling and tiny singlet-triplet energy gaps, together generating efficient ISC. These properties afford PFBT nanophotosensitizer a approximate to 2000-fold increase in two-photon photodynamic therapy efficiency than clinically-used Photofrin, enabling in vivo deep-brain cerebrovascular imaging and closure with unprecedented precision. Developing organic photosensitizers with both intense two-photon absorption and efficient intersystem crossing (ISC) for precise two-photon photodynamic therapy is always a formidable challenge. This study reports the simultaneous achievement of efficient ISC and intense two-photon absorption from a donor-acceptor organic photosensitizer for precise brain deep-brain two-photon photodynamic therapy.image