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. 2022 Feb 9;13:758. doi: 10.1038/s41467-022-28279-8

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Schematic of CXCR4-targeted p53 mRNA NPs and combinatorial strategy using anti-PD-1 therapy to reprogram the immunosuppressive tumor microenvironment for effective treatment of p53-deficient HCC. The combination of CTCE-p53 NPs and PD-1 blockade effectively and globally reprogrammed the immune TME of HCC, as indicated by activation of CD8⁺ T cells and NK cells, favorable polarization of TAMs towards the anti-tumor phenotype, and increased expression of anti-tumor cytokines. b Flow cytometric analysis of cellular uptake of CTCE-EGFP mRNA NPs with different CTCE peptide densities versus SCP-EGFP mRNA NPs with 5% SCP density in RIL-175 HCC cells (n = 3 cell samples/group). c Confocal fluorescence imaging of RIL-175 cell uptake of SCP-Cy5-Luciferase (Luc) mRNA NPs versus CTCE-Cy5-Luc mRNA NPs after 4 h treatment. Scale bar: 100 µm. d Effect of different cationic lipid-like materials G0-Cm on the transfection efficacy of Luc-mRNA NPs (mRNA concentration: 0.25 μg/mL, n = 3 samples/group). e TEM image of CTCE-mRNA NPs. Scale bar, 200 nm. f Average particle size and zeta potential of the p53 NPs, SCP-p53 NPs, and CTCE-p53 NPs (n = 3 samples/group). Data in b, d, and f are presented as mean values ± SD. For c and e: a representative image from one of five independent fields of view in a single experiment. Source data are provided as a Source Data file.