date: 2020-09-07T10:48:50Z
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pdf:docinfo:title: Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions
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subject: T-cells are a type of lymphocyte (a subtype of white blood cells) that play a central role in cell-mediated immunity. Currently, adoptive T-cell immunotherapy is being developed to destroy cancer cells. In this therapy, T-cells are harvested from a patient?s blood. After several weeks of growth in culture, tumor-specific T-cells can be reinfused into the same cancer patient. This technique has proved highly efficient in cancer treatment. However, there are several biological processes that can suppress the anti-cancer responses of T-cells, leading to a loss of their functionality and a reduction of their viability. Therefore, strategies are needed to improve T-cell survival and their functions. Here, a small interfering RNA (siRNA)-loaded nanocarrier was used to knockdown PD-L1, one of the most important proteins causing a loss in the functionality of T-cells. The biocompatibility and the cellular uptake of siRNA-loaded silica nanocapsules (SiNCs) were investigated in CD8+ T-cells. Then, the PD-L1 expression at protein and at mRNA levels of the treated cells were evaluated. Furthermore, the effect of the PD-L1 knockdown was observed in terms of cell proliferation and the expression of specific biomarkers CD25, CD69 and CD71, which are indicators of T-cell functions. The results suggest that this siRNA-loaded nanocarrier showed a significant potential in the delivery of siRNA into T-cells. This in turn resulted in enhanced T-cell survival by decreasing the expression of the inhibitory protein PD-L1. Such nanocarriers could, therefore, be applied in adoptive T-cell immunotherapy for the treatment of cancer.
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dc:title: Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions
modified: 2020-09-07T10:48:50Z
cp:subject: T-cells are a type of lymphocyte (a subtype of white blood cells) that play a central role in cell-mediated immunity. Currently, adoptive T-cell immunotherapy is being developed to destroy cancer cells. In this therapy, T-cells are harvested from a patient?s blood. After several weeks of growth in culture, tumor-specific T-cells can be reinfused into the same cancer patient. This technique has proved highly efficient in cancer treatment. However, there are several biological processes that can suppress the anti-cancer responses of T-cells, leading to a loss of their functionality and a reduction of their viability. Therefore, strategies are needed to improve T-cell survival and their functions. Here, a small interfering RNA (siRNA)-loaded nanocarrier was used to knockdown PD-L1, one of the most important proteins causing a loss in the functionality of T-cells. The biocompatibility and the cellular uptake of siRNA-loaded silica nanocapsules (SiNCs) were investigated in CD8+ T-cells. Then, the PD-L1 expression at protein and at mRNA levels of the treated cells were evaluated. Furthermore, the effect of the PD-L1 knockdown was observed in terms of cell proliferation and the expression of specific biomarkers CD25, CD69 and CD71, which are indicators of T-cell functions. The results suggest that this siRNA-loaded nanocarrier showed a significant potential in the delivery of siRNA into T-cells. This in turn resulted in enhanced T-cell survival by decreasing the expression of the inhibitory protein PD-L1. Such nanocarriers could, therefore, be applied in adoptive T-cell immunotherapy for the treatment of cancer.
pdf:docinfo:subject: T-cells are a type of lymphocyte (a subtype of white blood cells) that play a central role in cell-mediated immunity. Currently, adoptive T-cell immunotherapy is being developed to destroy cancer cells. In this therapy, T-cells are harvested from a patient?s blood. After several weeks of growth in culture, tumor-specific T-cells can be reinfused into the same cancer patient. This technique has proved highly efficient in cancer treatment. However, there are several biological processes that can suppress the anti-cancer responses of T-cells, leading to a loss of their functionality and a reduction of their viability. Therefore, strategies are needed to improve T-cell survival and their functions. Here, a small interfering RNA (siRNA)-loaded nanocarrier was used to knockdown PD-L1, one of the most important proteins causing a loss in the functionality of T-cells. The biocompatibility and the cellular uptake of siRNA-loaded silica nanocapsules (SiNCs) were investigated in CD8+ T-cells. Then, the PD-L1 expression at protein and at mRNA levels of the treated cells were evaluated. Furthermore, the effect of the PD-L1 knockdown was observed in terms of cell proliferation and the expression of specific biomarkers CD25, CD69 and CD71, which are indicators of T-cell functions. The results suggest that this siRNA-loaded nanocarrier showed a significant potential in the delivery of siRNA into T-cells. This in turn resulted in enhanced T-cell survival by decreasing the expression of the inhibitory protein PD-L1. Such nanocarriers could, therefore, be applied in adoptive T-cell immunotherapy for the treatment of cancer.
pdf:docinfo:creator: Raweewan Thiramanas, Mengyi Li, Shuai Jiang, Katharina Landfester and Volker Mailänder
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Creation-Date: 2020-09-07T10:48:50Z
Author: Raweewan Thiramanas, Mengyi Li, Shuai Jiang, Katharina Landfester and Volker Mailänder
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Keywords: siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake
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dc:creator: Raweewan Thiramanas, Mengyi Li, Shuai Jiang, Katharina Landfester and Volker Mailänder
dcterms:created: 2020-09-07T10:48:50Z
Last-Modified: 2020-09-07T10:48:50Z
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title: Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions
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pdf:docinfo:keywords: siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake
pdf:docinfo:modified: 2020-09-07T10:48:50Z
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creator: Raweewan Thiramanas, Mengyi Li, Shuai Jiang, Katharina Landfester and Volker Mailänder
dc:subject: siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake
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meta:keyword: siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake
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pdf:docinfo:created: 2020-09-07T10:48:50Z