Reactive oxygen species-responsive and Raman-traceable hydrogel combining photodynamic and immune therapy for postsurgical cancer treatment

Combining immune checkpoint blockade (ICB) therapy with photodynamic therapy (PDT) holds great potential in treating immunologically cold tumors, but photo-generated reactive oxygen species (ROS) can inevitably damage co-administered ICB antibodies, hence hampering the therapeutic outcome. Here we create a ROS-responsive hydrogel to realize the sustained co-delivery of photosensitizers and ICB antibodies. During PDT, the hydrogel skeleton poly(deca-4,6-diynedioic acid) (PDDA) protects ICB antibodies by scavenging the harmful ROS, and at the same time, triggers the gradual degradation of the hydrogel to release the drugs in a controlled manner. More interestingly, we can visualize the ROS-responsive hydrogel degradation by Raman imaging, given the ultrastrong and degradation-correlative Raman signal of PDDA in the cellular silent window. A single administration of the hydrogel not only completely inhibits the long-term postoperative recurrence and metastasis of 4T1-tumor-bearing mice, but also effectively restrains the growth of re-challenged tumors. The PDDA-based ROS-responsive hydrogel herein paves a promising way for the durable synergy of PDT and ICB therapy. Combined immune checkpoint blockade (ICB) and photodynamic therapies have huge potential but suffer from possible damage of the antibodies. Here, the authors create a ROS-responsive hydrogel that protects the ICB antibodies and allows for sustained co-delivery and demonstrate restrained regrowth of tumours in vivo.

Automated summary

Researchers have developed a ROS-responsive hydrogel that can protect ICB antibodies and allow for sustained co-delivery of photosensitizers and ICB antibodies. The hydrogel not only inhibits long-term tumor recurrence and metastasis, but also effectively restrains the growth of re-challenged tumors.