HIGHLIGHTS • The reaction mechanism of various kinds of nanomaterials with endogenous H 2 O 2 is outlined. • The design and application guideline for various H 2 O 2-responsive nanomaterials in photodynamic therapy (PDT) are reviewed. • The development and prospect of various H 2 O 2-response nanomaterials for PDT and clinical application are envisioned.
Developing smart photosensitizers sensitively responding to tumor-specific signals for reduced side effects and enhanced anticancer efficacy is a major challenge for tumor phototherapy. Herein, a pH-sensitive photosensitizer has been synthesized through introducing a pH-sensitive receptor (dimethylaminophenyl unit) onto the aza-BODIPY core (abbreviated as NAB). Through enveloping hydrophobic NAB with amphiphilic DSPE-mPEG 2000 , NAB nanoparticles (NPs, diameter ∼ 30 nm) with strong near-infrared absorption (∼792 nm) are obtained. NAB NPs can be activated in weak acidic environment to give high rate of reactive oxygen species (ROS) generation and enhanced photothermal effect. NAB NPs can selectively accumulate in the lysosomes of tumor cells and subsequently activate under the acidic microenvironment of lysosome (pH 5.0) to produce ROS for photodynamic therapy, due to switch-off of the photoinduced electron transfer (PET) pathway. In vivo, pH-enhanced photoacoustic imaging (PAI) and photothermal imaging (PTI) confirm that NAB NPs can selectively aggregate in the tumor, and the tumor growth can be effectively inhibited under xenon lamp irradiation through synergistic phototherapy (photodynamic and photothermal therapy, PDT/PTT). Furthermore, based on PAI signal and terminal elimination half-life (T 1/2 ) obtained by pharmacokinetic experiment, it is concluded that the NAB NPs can be rapidly metabolized. The pH-sensitive NAB NPs offer a new possibility toward PAI and PTI guided synergistic phototherapy.
A heavy-atom-free photosensitizer (C60-RB) with pH-activable visible-light absorbance enhancement, fluorescence turn-on and triplet excited state generation was designed for tumor bioimaging and photodynamic therapy.
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