A combination strategy based on an Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promote a positive shift in the cancer-immunity cycle
Autor: | Shuang Zhang, Jing-Ru Wang, Zhuo-Yue Li, Mei-Qi Xu, Xuan Zhang, Shuai-Qiang Zhang, Zhen-Han Feng, Guang-Xue Wang, Ai Liao, Hui Li, Zhan-Tao Li |
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Rok vydání: | 2021 |
Předmět: |
Photothermal Therapy
medicine.medical_treatment Antigen presentation Biomedical Engineering Melanoma Experimental Biochemistry B7-H1 Antigen Biomaterials Antigen Cell Line Tumor medicine Animals Doxorubicin Molecular Biology Nanotubes Chemistry General Medicine Immunotherapy Photothermal therapy Tumor antigen Mice Inbred C57BL Drug delivery Liposomes Cancer research Immunogenic cell death Female Biotechnology medicine.drug |
Zdroj: | Acta biomaterialia. 136 |
ISSN: | 1878-7568 |
Popis: | The antitumor immune response involves a cascade of cancer-immunity cycles. Developing a combination therapy aimed at the cancer-immunity cycle is of great importance. In this research, we designed and tested a combined therapeutic-Au nanorod (AuNR)/doxorubicin (DOX) gel (AuNR/DOX gel)-in which the sustained release of DOX was controlled by Pluronic gel. DOX served as an immunogenic tumor cell death (ICD) inducer, triggering the production of damage-associated molecular patterns (DAMPs). Mild photothermal therapy (Mild PTT) produced by 880 nm laser-irradiated AuNRs also generated tumor-associated antigens. Maleimide-modified liposomes (L-Mals), as antigen capturing agents, promoted tumor antigen uptake by DCs. Ultimately, more CD8+ T cells and fewer regulatory T cells (Tregs) infiltrated the tumor, eliciting antitumor responses from the PD-L1 antibody. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system. STATEMENT OF SIGNIFICANCE: Developing a combination therapy for cancer-immunity cycle is of great importance due to antitumor immune response involving a cascade of cancer-immunity cycles. Cancer-immunity cycle usually includes tumor antigen release, antigen presentation, immune activation, trafficking, infiltration, specific recognition of tumor cells by T cells, and finally cancer cell killing. In this research, we designed a combination strategy based on Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promoting a positive shift in the cancer-immunity cycle. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system. |
Databáze: | OpenAIRE |
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