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Article

Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions

1
Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
2
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(9), 2043; https://doi.org/10.3390/cells9092043
Received: 18 July 2020 / Revised: 31 August 2020 / Accepted: 31 August 2020 / Published: 7 September 2020
(This article belongs to the Special Issue Nanoparticles in Cancer Immunotherapy)
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. View Full-Text
Keywords: siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake siRNA; PD-L1; T-cells; adoptive immunotherapy; nanocarriers; cellular uptake
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MDPI and ACS Style

Thiramanas, R.; Li, M.; Jiang, S.; Landfester, K.; Mailänder, V. Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions. Cells 2020, 9, 2043. https://doi.org/10.3390/cells9092043

AMA Style

Thiramanas R, Li M, Jiang S, Landfester K, Mailänder V. Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions. Cells. 2020; 9(9):2043. https://doi.org/10.3390/cells9092043

Chicago/Turabian Style

Thiramanas, Raweewan, Mengyi Li, Shuai Jiang, Katharina Landfester, and Volker Mailänder. 2020. "Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions" Cells 9, no. 9: 2043. https://doi.org/10.3390/cells9092043

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