Versatile albumin as a booster to optimize the excited state energy redistribution in photosensitizers enabling fluorescence imaging-guided photodynamic therapy

Selectively transforming the non-radiative pathway of excited-state photosensitizers (PSs) into radiative and intersystem crossing (ISC) processes is crucial for fluorescence imaging-guided photodynamic therapy (PDT). Herein, human serum albumin (HSA), with abundant amino acid residues, was co-assembled with anion-π + PSs ( An-O , AnS-O , and AnSS-O ) to create PSs-albumin complexes ( An-O@HSA , AnS-O@HSA , and AnSS-O@HSA ), resulting in promoted biocompatibility and colloidal stability. Both in vitro and in vivo assessments demonstrated that AnSS-O@HSA exhibited the highest-performance fluorescence emission and superoxide anion (O 2 ‑• ) generation capacity, which can effectively induce enhanced apoptosis in HepG2 cells. In-depth mechanistic investigations revealed that HSA, functioning as a boosting agent, could effectively suppress nonradiative decay channels and prolong the triplet state lifetime of PSs. Additionally, HSA can also serve as an electronic reservoir, augmenting its photocurrent response, which further promoted the fluorescence imaging-guided PDT. This study presented a facile strategy for controlling the energy dissipation pathways in the excited state of PSs.