دورية أكاديمية
Hyaluronic acid-bilirubin nanomedicine-based combination chemoimmunotherapy
| العنوان: | Hyaluronic acid-bilirubin nanomedicine-based combination chemoimmunotherapy |
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| المؤلفون: | Lee, Yonghyun, Shinn, Jongyoon, Xu, Cheng, Dobson, Hannah E., Neamati, Nouri, Moon, James J. |
| المساهمون: | U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research, U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases, U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke, U.S. Department of Health & Human Services | NIH | National Cancer Institute, National Research Foundation of Korea (NRF) funded by the Ministry of Education |
| المصدر: | Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Despite significant advances in immune checkpoint blockade (ICB), immunosuppression mediated by tumor-associated myeloid cells (TAMCs) poses a major barrier to cancer immunotherapy. In addition, while immunogenic cell death (ICD) provides a viable approach to inducing anti-tumor immune response, it remains unknown how to effectively trigger ICD while addressing immunosuppressive TAMCs. Here, we show that SC144, a gp130 inhibitor that blocks the IL-6/gp130/STAT3 pathway, induces ICD of tumor cells and polarizes macrophages to M1-phenotype in vitro. However, as SC144 also induces killing of CD8 + T-cells, we sought to deliver SC144 selectively to tumor cells and TAMCs. Toward this goal, we have developed hyaluronic acid-bilirubin nanoparticles (HABN) that accumulate in CD44 hi tumor cells and TAMCs. Systemic administration of SC144 loaded in HABN (SC144@HABN) induces apoptosis and ICD of tumor cells, increases the ratio of M1-like to M2-like macrophages, and decreases the frequency of myeloid-derived suppressor cells and CD4 + regulatory T-cells, while promoting anti-tumor CD8 + T-cells. Moreover, SC144@HABN combined with anti-PD-L1 ICB efficiently eliminates MC38 tumors and ICB-resistant 4T1 tumors. Overall, our work demonstrates a therapeutic strategy based on coordinated ICD induction and TAMC modulation and highlights the potential of combination chemoimmunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-40270-5 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-40270-5Test https://www.nature.com/articles/s41467-023-40270-5.pdfTest https://www.nature.com/articles/s41467-023-40270-5Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.EDBED994 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-40270-5 |
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