بزرگنمایی دو انگشتی

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نویسندگان: Mehdi Barati

زمان بندی: بدون زمان بندی

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برچسب: Nanomedicine

خلاصه مقاله: Programmed cell death protein-1 (PD-1), as an immune....

Programmed cell death protein-1 (PD-1), as an immune checkpoint molecule, attenuates T cell activity and induces T cell exhaustion. Although siRNA has a great potential in cancer immunotherapy, its delivery to target cells is the main limitation of using siRNA. This study aimed to prepare a liposomal formulation as a siRNA carrier to silence PD-1 expression in T cells and investigate its in vivo antitumor efficacy. The liposomal siRNA was prepared and characterized by size, zeta potential, and biodistribution. Following that, the uptake assay and mRNA silencing were evaluated in vitro at mRNA and protein levels. siRNA-PD-1 (siPD-1)-loaded liposome nanoparticles were injected into B16F0 tumor-bearing mice to evaluate tumor growth, tumor-infiltrating lymphocytes, and survival rate. Liposomal siPD-1 efficiently silenced PD-1 mRNA expression in T cells (P<0.0001), and siPD-1-loaded liposomal nanoparticles enhanced the infiltration of T helper 1 (Th 1) and cytotoxic T lymphocytes into the tumor tissue (P<0.0001). Liposome-PD-1 siRNA monotherapy and PD-1 siRNA-Doxil (Liposomal Doxorubicin) combination therapy improved the survival significantly, compared to the control treatment (P<0.001). Overall, these findings suggest that immunotherapy with siPD-1-loaded liposomes by enhancing T cell-mediated anti-tumor immune responses could be considered as a promising strategy for the treatment of melanoma cancer.


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