Academic Journal
Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma
| العنوان: | Ultra-thin layered double hydroxide-mediated photothermal therapy combine with asynchronous blockade of PD-L1 and NR2F6 inhibit hepatocellular carcinoma |
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| المؤلفون: | Lu, Yuan-Fei, Zhou, Jia-Ping, Zhou, Qiao-Mei, Yang, Xiao-Yan, Wang, Xiao-Jie, Yu, Jie-Ni, Zhang, Jin-Guo, Du, Yong-Zhong, Yu, Ri-Sheng |
| المساهمون: | National Natural Science Foundation of China, Natural Science Foundation of Zhejiang Province |
| المصدر: | Journal of Nanobiotechnology ; volume 20, issue 1 ; ISSN 1477-3155 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| الوصف: | Background The efficacy of immune checkpoint blockade (ICB), in the treatment of hepatocellular carcinoma (HCC), is limited due to low levels of tumor-infiltrating T lymphocytes and deficient checkpoint blockade in this immunologically "cool" tumor. Thus, combination approaches are needed to increase the response rates of ICB and induce synergistic antitumor immunity. Methods Herein, we designed a pH-sensitive multifunctional nanoplatform based on layered double hydroxides (LDHs) loaded with siRNA to block the intracellular immune checkpoint NR2F6, together with the asynchronous blockade surface receptor PD-L1 to induce strong synergistic antitumor immunity. Moreover, photothermal therapy (PTT) generated by LDHs after laser irradiation modified an immunologically “cold” microenvironment to potentiate Nr2f6 -siRNA and anti-PD-L1 immunotherapy. Flow cytometry was performed to assess the immune responses initiated by the multifunctional nanoplatform. Results Under the slightly acidic tumor extracellular environment, PEG detached and the re-exposed positively charged LDHs enhanced tumor accumulation and cell uptake. The accumulated siRNA suppressed the signal of dual protumor activity in both immune and H22 tumor cells by silencing the NR2F6 gene, which further reduced the tumor burden and enhanced systemic antitumor immunity. The responses include enhanced tumor infiltration by CD4 + helper T cells, CD8 + cytotoxic T cells, and mature dendritic cells; the significantly decreased level of immune suppressed regulator T cells. The therapeutic responses were also attributed to the production of IL-2, IFN-γ, and TNF-α. The prepared nanoparticles also exhibited potential magnetic resonance imaging (MRI) ability, which could serve to guide synergistic immunotherapy treatment. Conclusions In summary, the three combinations of PTT, NR2F6 gene ablation and anti-PD-L1 can promote a synergistic immune response to inhibit the progression of primary HCC tumors and prevent metastasis. This study can be considered a ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12951-022-01565-9 |
| DOI: | 10.1186/s12951-022-01565-9.pdf |
| DOI: | 10.1186/s12951-022-01565-9/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12951-022-01565-9 https://link.springer.com/content/pdf/10.1186/s12951-022-01565-9.pdf https://link.springer.com/article/10.1186/s12951-022-01565-9/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.6DE77B92 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12951-022-01565-9 |
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