Gao, X. Empower the age of smart mRNA medicine: programmable RNA sensor and molecular tools refine therapeutic payload production. Science 388, 40–41 (2025).
Sayour, E. J., Boczkowski, D., Mitchell, D. A. & Nair, S. K. Cancer mRNA vaccines: clinical advances and future opportunities. Nat. Rev. Clin. Oncol. 21, 489–500 (2024).
Moon, C. Y. et al. Dendritic cell maturation in cancer. Nat. Rev. Cancer 25, 225–248 (2025).
Luri-Rey, C. et al. Cross-priming in cancer immunology and immunotherapy. Nat. Rev. Cancer 25, 249–273 (2025).
Wang, X. et al. STING agonist-based ER-targeting molecules boost antigen cross-presentation. Nature. https://doi.org/10.1038/s41586-025-08758-w (2025).
Zhang, Y. et al. Close the cancer-immunity cycle by integrating lipid nanoparticle-mRNA formulations and dendritic cell therapy. Nat. Nanotechnol. 18, 1364–1374 (2023).
Liu, C. et al. mRNA-based cancer therapeutics. Nat. Rev. Cancer. https://doi.org/10.1038/s41568-023-00586-2 (2023).
Zong, Y., Lin, Y., Wei, T. & Cheng, Q. Lipid nanoparticle (LNP) enables mRNA delivery for cancer therapy. Adv. Mater. e2303261. https://doi.org/10.1002/adma.202303261 (2023).
Tenchov, R., Bird, R., Curtze, A. E. & Zhou, Q. Lipid nanoparticles horizontal line from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 15, 16982–17015 (2021).
Yang, W., Mixich, L., Boonstra, E. & Cabral, H. Polymer-based mRNA delivery strategies for advanced therapies. Adv. Healthc. Mater. 12, e2202688 (2023).
Guo, X. et al. A Polymeric mRNA vaccine featuring enhanced site-specific mRNA delivery and inherent STING-stimulating performance for tumor immunotherapy. Adv. Mater. e2410998. https://doi.org/10.1002/adma.202410998 (2025).
Wan, B., Bao, Q. & Burgess, D. Long-acting PLGA microspheres: Advances in excipient and product analysis toward improved product understanding. Adv. Drug Deliv. Rev. 198, 114857 (2023).
Zhang, Z. et al. Induction of anti-tumor cytotoxic T cell responses through PLGA-nanoparticle mediated antigen delivery. Biomaterials 32, 3666–3678 (2011).
Wang, Y. et al. Versatile PLGA-based drug delivery systems for tumor immunotherapy. Small Methods, e2401623, https://doi.org/10.1002/smtd.202401623 (2025).
Pakulska, M. M., Miersch, S. & Shoichet, M. S. Designer protein delivery: From natural to engineered affinity-controlled release systems. Science 351, aac4750 (2016).
Harguindey, A. et al. Synthesis and assembly of click-nucleic-acid-containing PEG-PLGA nanoparticles for DNA delivery. Adv Mater 29, https://doi.org/10.1002/adma.201700743 (2017).
Bus, T., Traeger, A. & Schubert, U. S. The great escape: how cationic polyplexes overcome the endosomal barrier. J. Mater. Chem. B 6, 6904–6918 (2018).
Wojnilowicz, M., Glab, A., Bertucci, A., Caruso, F. & Cavalieri, F. Super-resolution imaging of proton sponge-triggered rupture of endosomes and cytosolic release of small interfering RNA. ACS Nano 13, 187–202 (2019).
Lam, K. et al. Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications. Adv. Mater. 35, e2209624 (2023).
Fenton, O. S. et al. Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery. Adv. Mater. 28, 2939–2943 (2016).
Li, H. et al. Endoplasmic reticulum localization of poly(omega-aminohexyl methacrylamide)s conjugated with (L-)-arginines in plasmid DNA delivery. B. iomaterials 34, 7923–7938 (2013).
Reilly, M. J., Larsen, J. D. & Sullivan, M. O. Polyplexes traffic through caveolae to the Golgi and endoplasmic reticulum en route to the nucleus. Mol. Pharm. 9, 1280–1290 (2012).
Qiu, C. et al. Regulating intracellular fate of siRNA by endoplasmic reticulum membrane-decorated hybrid nanoplexes. Nat. Commun. 10, 2702 (2019).
Buton, X., Morrot, G., Fellmann, P. & Seigneuret, M. Ultrafast glycerophospholipid-selective transbilayer motion mediated by a protein in the endoplasmic reticulum membrane. J. Biol. Chem. 271, 6651–6657 (1996).
Puri, S. & Linstedt, A. D. Capacity of the golgi apparatus for biogenesis from the endoplasmic reticulum. Mol. Biol. Cell 14, 5011–5018 (2003).
Liu, X. et al. Breaking spatiotemporal barriers of immunogenic chemotherapy via an endoplasmic reticulum membrane-assisted liposomal drug delivery. ACS Nano 17, 10521–10534 (2023).
Lorentzen, C. L., Haanen, J. B., Met, O. & Svane, I. M. Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Lancet Oncol. 23, e450–e458 (2022).
Han, R., Wang, Y. & Lu, L. Sensitizing the efficiency of ICIs by neoantigen mRNA vaccines for HCC Ttreatment. Pharmaceutics 16, https://doi.org/10.3390/pharmaceutics16010059 (2023).
Couzinet, A., Suzuki, T. & Nakatsura, T. Progress and challenges in glypican-3 targeting for hepatocellular carcinoma therapy. Expert Opin. Ther. Targets 28, 895–909 (2024).
Capurro, M. et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology 125, 89–97 (2003).
Filmus, J. & Selleck, S. B. Glypicans: proteoglycans with a surprise. J. Clin. Investig. 108, 497–501 (2001).
Schepers, E. J., Glaser, K., Zwolshen, H. M., Hartman, S. J. & Bondoc, A. J. Structural and functional impact of posttranslational modification of glypican-3 on liver carcinogenesis. Cancer Res. 83, 1933–1940 (2023).
Zhou, F., Shang, W., Yu, X. & Tian, J. Glypican-3: a promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med. Res. Rev. 38, 741–767 (2018).
Xia, L., Teng, Q., Chen, Q. & Zhang, F. Preparation and characterization of anti-GPC3 nanobody against hepatocellular carcinoma. Int J. Nanomed. 15, 2197–2205 (2020).
Li, D. et al. Persistent polyfunctional chimeric antigen receptor t cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in Mice. Gastroenterology 158, 2250–2265 e2220 (2020).
Dargel, C. et al. T cells engineered to express a T-cell receptor specific for glypican-3 to recognize and kill hepatoma cells in vitro and in Mice. Gastroenterology 149, 1042–1052 (2015).
Fang, R. H., Gao, W. & Zhang, L. Targeting drugs to tumours using cell membrane-coated nanoparticles. Nat. Rev. Clin. Oncol. 20, 33–48 (2023).
Rao, L. et al. A biomimetic nanodecoy traps zika virus to prevent viral infection and fetal microcephaly development. Nano Lett. 19, 2215–2222 (2019).
Li, H. et al. Endoplasmic reticulum localization of poly(ω-aminohexyl methacrylamide)s conjugated with (L-)-arginines in plasmid DNA delivery. Biomaterials 34, 7923–7938 (2013).
Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 596, 109–113 (2021).
Zhang, M. et al. Axillary lymphadenopathy in the COVID-19 era: what the radiologist needs to know. Radiogr Rev. Publ. Radiol. Soc. North Am. Inc. 42, 1897–1911 (2022).
Yang, R. et al. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat. Commun. 12, 832 (2021).
Chen, C. et al. Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8(+) T cell exhaustion and anti-PD-1 resistance. Cell Rep. Med. 5, 101686 (2024).
Yan, Z., Wang, C., Wu, J., Wang, J. & Ma, T. TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives. Mol. Biomed. 6, 27 (2025).
Schietinger, A. & Greenberg, P. D. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 35, 51–60 (2014).
Koerner, J. et al. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. Nat. Commun. 12, 2935 (2021).
Bettigole, S. E. & Glimcher, L. H. Endoplasmic reticulum stress in immunity. Annu. Rev. Immunol. 33, 107–138 (2015).
