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 (σ) 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 σ. Here, very efficient ISC and ultrahigh σ 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 σ 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 ≈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.