Enhancing PD-1 Gene Silence in T Lymphocytes by Comparing the Delivery Performance of Two Inorganic Nanoparticle Platforms

Yanheng Wu; Wenyi Gu; Li Li; Chen Chen; Zhi Ping Xu

doi:10.3390/nano9020159

Enhancing PD-1 Gene Silence in T Lymphocytes by Comparing the Delivery Performance of Two Inorganic Nanoparticle Platforms

Nanomaterials (Basel). 2019 Jan 28;9(2):159. doi: 10.3390/nano9020159.

Authors

Yanheng Wu¹, Wenyi Gu², Li Li³, Chen Chen⁴, Zhi Ping Xu⁵

Affiliations

¹ Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St. Lucia 4072, QLD, Australia. yanheng.wu@uq.net.au.
² Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St. Lucia 4072, QLD, Australia. w.gu@uq.edu.au.
³ Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St. Lucia 4072, QLD, Australia. l.li2@uq.edu.au.
⁴ School of Biomedical Sciences, the University of Queensland, St. Lucia 4072, QLD, Australia. chen.chen@uq.edu.au.
⁵ Australian Institute for Bioengineering and Nanotechnology, the University of Queensland, St. Lucia 4072, QLD, Australia. gordonxu@uq.edu.au.

Abstract

Suitable carriers are crucial to RNAi applications for cancer genotherapy and T-cell immunotherapy. In this research, we selected two extensively-investigated biocompatible inorganic nanoparticle carriers, i.e., layered double hydroxide (LDH) and lipid-coated calcium phosphate (LCP) and then compared their efficacy for siRNA delivery in T cells, in order to understand which carrier is more efficient in delivering functional programmed cell death protein 1 siRNA (PD-1 siRNA) to suspended T lymphocytes. Both LDH and LCP nanoparticles quickly delivered gene segment to mouse T cell lines (EL4), while the LCP nanoparticles exhibited more cellular uptake and higher PD-1 gene silence efficiency. We further demonstrated that LCP nanoparticles successfully reduced the expression of PD-1 in human ex vivo tumor infiltrating lymphocytes (TILs). Thus, LCP nanoparticles can be used as a better nano-carrier for gene therapy in lymphocytes, especially in regards to TIL-related cancer immunotherapy.

Keywords: EL4 cells; PD-1 gene silencing; human tumor infiltrating lymphocytes (TILs); layered double hydroxide (LDH) nanoparticle; lipid-coated calcium phosphate (LCP) nanoparticle; programmed cell death protien-1 (PD-1).