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

Yiyi Zhang, Sidan Tian, Liping Huang, Yanan Li, Yuan Lu, Hongyu Li, Guiping Chen, Fanling Meng, Gang L. Liu, Xiangliang Yang, Jiasheng Tu, Chunmeng Sun and Liang Luo ()
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Yiyi Zhang: Huazhong University of Science and Technology
Sidan Tian: Huazhong University of Science and Technology
Liping Huang: Huazhong University of Science and Technology
Yanan Li: China Pharmaceutical University
Yuan Lu: Huazhong University of Science and Technology
Hongyu Li: Huazhong University of Science and Technology
Guiping Chen: Bruker (Beijing) Scientific Technology Company Limited, Shanghai Branch
Fanling Meng: Huazhong University of Science and Technology
Gang L. Liu: Huazhong University of Science and Technology
Xiangliang Yang: Huazhong University of Science and Technology
Jiasheng Tu: China Pharmaceutical University
Chunmeng Sun: China Pharmaceutical University
Liang Luo: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32160-z

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