Enhanced antitumor immune response in melanoma tumor model by anti-PD-1 small interference RNA encapsulated in nanoliposomes.

Abstract

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 it's 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 antitumor immune responses could be considered as a promising strategy for the treatment of melanoma cancer.

• Authors: Mehdi Barati, Farshad Mirzavi, Amin Reza Nikpoor, Mojtaba Sankian, Hasan Namdar Ahmadabad, Anvar Soleimani, Mohammad Mashreghi, Jalil Tavakol Afshar, Mojgan Mohammadi, Mahmoud Reza Jaafari
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 29 Issue 6 Pg. 814-824 (06 2022) ISSN: 1476-5500 [Electronic] England
• PMID: 34341501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Liposomes
• Programmed Cell Death 1 Receptor
• RNA, Messenger
• RNA, Small Interfering

Topics

• Animals
• Cell Line, Tumor
• Humans
• Immunity
• Liposomes
• Melanoma (genetics, therapy)
• Mice
• Programmed Cell Death 1 Receptor (genetics, metabolism)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Tissue Distribution