Light triggered release of a triple action porphyrin-cisplatin conjugate evokes stronger immunogenic cell death for chemotherapy, photodynamic therapy and cancer immunotherapy

Abstract

Photodynamic therapy (PDT) has emerged as an attractive therapeutic approach which can elicit immunogenic cell death (ICD). However, current ICD inducers are still very limited as the representative ICD induces of photosensitizers can only evoke insufficient ICD to achieve unsatisfactory cancer immunotherapy. Herein, we demonstrated the use of a triple action cationic porphyrin-cisplatin conjugate (Pt-1) for drug delivery by a reactive oxygen species (ROS) sensitive polymer as nanoparticles (NP@Pt-1) for combined chemotherapy, PDT and immunotherapy. This unique triple action Pt-1 contains both chemotherapeutic Pt drugs and Porphyrin as a photosensitizer to generate ROS for PDT. Moreover, the ROS generated by Pt-1 can on the one hand degrade polymer carriers to release Pt-1 for chemotherapy and PDT. On the other hand, the ROS generated by Pt-1 subsequently triggered the ICD cascade for immunotherapy. Taken together, we demonstrated that NP@Pt-1 were the most effective and worked in a triple way. This study could provide us with new insight into the development of nanomedicine for chemotherapy, PDT as well as cancer immunotherapy.

Amplifying “eat me signal” by immunogenic cell death for potentiating cancer immunotherapy

“…Porphyrin is among the most frequently applied photosensitizers with high ROS production. Light induced release of a triple action porphyrin‐cisplatin conjugate evokes potent ICD cascade for combined chemotherapy, PDT and immunotherapy 105 . However, strong dark toxicity of porphyrin hinders its clinical application.…”

Development of Biotechnological Photosensitizers for Photodynamic Therapy: Cancer Research and Treatment—From Benchtop to Clinical Practice

“…Several works have used porphyrin derivatives for application in PDT in the treatment of cancer [ 55 , 56 ]. Lu et al tested the nanoscale metal–organic structure combination of Hf-porphyrin DBP-UiO (DBP-UiO NMOF) as a strategy for application in PDT in the treatment of head and neck cancer.…”

“…The conjugate composed by the association of porphyrin with cisplatin incorporated in polymeric nanocarriers (NP@Pt-1) was tested in vitro and in vivo. They observed cell death and ROS generation capable of inducing immunogenic cell death, a promising effect for application in other types of cancer and with other chemotherapeutic agents [ 56 ].…”

Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy

“…15 Additionally, the -CN group can coordinate with cisplatin to create coordination complexes that improve the efficacy of photodynamic therapy (PDT). [16][17][18][19][20]…”