期刊
JOURNAL OF CONTROLLED RELEASE
卷 337, 期 -, 页码 90-104出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.07.021
关键词
Chemo-photodynamic therapy; Cancer cell membranes; CD73 blockade; Antitumor immunity; Tumor metastasis
资金
- Natural Science Foundation of Zhejiang Province [LD21H300002]
- National Key Research and Devel-opment projects Intergovernmental Cooperation in Science and Tech-nology of China [2018YFE0126900]
The combined application of anti-CD73 antibody and chemo-PDT can enhance the anti-metastatic effects of T cell-mediated antitumor immunity synergistically. This strategy not only prevents abscopal tumor metastasis but also induces a series of immunogenic cell death, leading to tumor-specific immunity.
Photodynamic therapy (PDT) and chemotherapy show clinical promise in destroying orthotopic tumors but are insufficient against abscopal metastases. The research reports the combined application of an anti-CD73 antibody and chemo-PDT to synergistically amplify the anti-metastatic effects of T cell-mediated antitumor immunity. The cancer cell membrane (CM)-cloaked upconversion nanoparticles, integrating rose bengal (RB) and the reactive oxygen species (ROS)-sensitive polymer polyethylene glycol-thioketal-doxorubicin (PEG-TK-DOX, i.e., PTD), are tailored for near-infrared (NIR)-triggered chemo-PDT. CM camouflage enables nanoparticles' excellent tumortargeting abilities and immune escape from macrophages. The combination of PDT and chemotherapy presents strong synergistic antitumor efficacy and synchronously causes a series of immunogenic cell death (ICD), leading to tumor-specific immunity. The anti-CD73 antibody prevents the immunosuppression phenomenon in tumors by blocking the adenosine pathway, and it is emerging as a sufficient immune checkpoint blockade when combined with ICD-elicited tumor therapies. As cancer membrane camouflaged nanoparticles CM@UCNP-RB/ PTD combined with anti-CD73 antibodies, synergistic efficacy of chemotherapy and PDT not only destroys the orthotopic tumors by DOX and cytotoxic ROS but also prevents abscopal tumor metastasis via inducing systemic cytotoxic T cell responses with CD73 blockade. This strategy is promising in curing metastatic triple-negative breast cancer in preclinical research.
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