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.
Highlights
RNAi technology has been examined for enhanced cancer immunotherapy in combination with other therapies [1,2,3,4]
We further demonstrated that lipid-coated calcium phosphate (LCP) nanoparticles successfully reduced the expression of programmed death 1 (PD-1) in human ex vivo tumor infiltrating lymphocytes (TILs)
To overcome poor colloidal stability due to aggregation in biological media for in vivo applications, we recently developed an approach to coating bovine serum albumin (BSA) on layered double hydroxide (LDH) nanoparticles (BSA-LDH), which colloidally stabilizes the LDH NPs in various electrolyte solutions and media [20,21]
Summary
RNAi technology has been examined for enhanced cancer immunotherapy in combination with other therapies [1,2,3,4]. Silencing programmed death ligand 1 (PD-L1) on the surface of cancer cells is able to induce higher T-cell immunity and enhance the therapeutic efficacy in combination with photodynamic therapy [4] To this end, many research inquiries have been conducted to knockdown PD-L1 expression on tumor cells, while silencing programmed death 1 (PD-1) on the surface of T cells is rarely investigated. More advantages of LDH NPs as delivery vehicles include the low toxicity, protection of payloads, and their high cellular delivery efficacy [7,10,17,19] These properties enable LDH NPs to become a good option for the cellular delivery of DNAs or RNAs. to overcome poor colloidal stability due to aggregation in biological media for in vivo applications, we recently developed an approach to coating bovine serum albumin (BSA) on LDH nanoparticles (BSA-LDH), which colloidally stabilizes the LDH NPs in various electrolyte solutions and media [20,21]
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