Photodynamic therapy (
PDT) is a noninvasive and effective approach for
cancer treatment. The main bottlenecks of clinical
PDT are poor selectivity of
photosensitizer and inadequate
oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated
reactive oxygen species (ROS) strategy using activatable
human serum albumin-
chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting
PDT against
cancer is developed. Through intermolecular
disulfide bond crosslinking and hydrophobic interaction, Ce6
photosensitizer is effectively loaded into the HSA
NAs, and the obtained HSA-Ce6
NAs exhibit excellent reduction response, as well as enhanced
tumor accumulation and retention. By the precision control of the overall body temperature instead of local
tumor temperature increasing from 37 °C to 43 °C, the
photosensitization reaction rate of HSA-Ce6
NAs increases 20%, and the oxygen saturation of
tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting
PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of
porphyrin ring can endow the HSA-Ce6
NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared
laser, the
tumors are completely suppressed without
tumor recurrence and
therapy-induced side effects. The robust thermal-modulated ROS strategy combined with
albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided
PDT and clinical translation.