A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity.

Background: The discovery of a potent photosensitizer with desirable immunogenic cell death (ICD) ability can prominently enhance antitumor immunity in photodynamic therapy (PDT). However, majority of commercially-available photosensitizers suffer from serious aggregation and fail to elicit sufficient ICD. Pyroptosis as a newly identified pattern for potent ICD generation is rarely disclosed in reported photosensitizers. In addition, the photosensitizer with excellent mitochondria-anchored ability evokes prominent mitochondria oxidative stress, and consequently induces ICD.

Results: Herein, a novel supramolecular photosensitizer LDH@ZnPc is reported, without complicated preparation, but reveals desirable pyroptosis-triggered ability with mitochondria anchoring feature. LDH@ZnPc is obtained through isolation of ZnPc using positive charged layered double hydroxides (LDH), and excellent mitochondria-anchored ability is achieved. More importantly, LDH@ZnPc-mediated PDT can effectively initiate gasdermin D (GSDMD)-dependent pyroptosis of tumor cells. In vitro and in vivo results verify robust ICD ability and potent tumor inhibition efficacy, and antitumor immunity towards distant tumor inhibition.

Conclusions: This study reveals that LDH@ZnPc can act as an excellent pyroptosis inducer with simultaneous mitochondria anchoring ability for enhancing photodynamic therapy and boosting antitumor immunity.