Journal
BIOMATERIALS
Volume 223, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119469
Keywords
Cascade chemo-PDT; ROS-Sensitive hybrid nanoparticle; Checkpoint blockade immunotherapy; Cascade ICD-Inducing modalities; Cancer immunotherapy
Funding
- National Key R&D Program of China [2017YFA0205601]
- National Natural Science Foundation of China [51822302, 51773067, 81773580]
- Program for Guangdong Introducing Innovative and Enterpreneurial Teams [2017ZT07S054]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2017B030306002]
- outstanding Scholar Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory [2018GZR110102001]
- Fundamental Research Funds for the Central Universities
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Checkpoint inhibitors, such as and-PD-1/PD-L1 antibodies, have been proven as a promising type of immunotherapy in a number of cancers, but the relatively low response rates limit their scope of clinical application. Here, we report the use of cascade chemo-photodynamic therapy (chemo-PDT) with reactive oxygen species (ROS)-sensitive lipid-polymer hybrid nanoparticles (HNP)-H-TK-C/D to potentiate the antitumor efficacy of anti-PD-1.1 antibody (aPD-L1). Under light irradiation, (HNP)-H-TK-C/D not only induced photodynamic therapy (PDT) but also boosted intracellular DOX release via the rapid degradation of its hydrophobic core, promoting an efficient cascade of chemo-PDT to inhibit tumor growth by a single treatment. More importantly, the cascade chemo-PDT could evoke anticancer immune responses and efficiently synergize with aPD-L1 to generate an abscopal effect, which could simultaneously inhibit primary and distant tumor growth.
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