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

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-09, Vol.9 (9), p.2043
• Main Authors: Thiramanas, Raweewan, Li, Mengyi, Jiang, Shuai, Landfester, Katharina, Mailänder, Volker
• Format: Article
• Language: English
• Subjects: adoptive immunotherapy; Antigens; Aqueous solutions; B7-H1 Antigen - metabolism; Biocompatibility; Cancer; CD25 antigen; CD69 antigen; CD8 antigen; Cell culture; Cell proliferation; Cell survival; Cell-mediated immunity; cellular uptake; Cloning; Cytotoxicity; Dendritic cells; FDA approval; Genetic aspects; Health aspects; Humans; Immune system; Immunotherapy; Immunotherapy, Adoptive - methods; Leukocytes; Lymphocytes T; Medical research; Methods; mRNA; nanocarriers; Nanotechnology - methods; PD-L1; PD-L1 protein; Proteins; RNA sequencing; RNA, Small Interfering - metabolism; siRNA; Surfactants; T cells; T-Lymphocytes - metabolism
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9092043

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.