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Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects

Nature Reviews Clinical Oncology volume 20, pages 739–754 (2023)Cite this article

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Abstract

Harnessing mRNA–lipid nanoparticles (LNPs) to treat patients with cancer has been an ongoing research area that started before these versatile nanoparticles were successfully used as COVID-19 vaccines. Currently, efforts are underway to harness this platform for oncology therapeutics, mainly focusing on cancer vaccines targeting multiple neoantigens or direct intratumoural injections of mRNA–LNPs encoding pro-inflammatory cytokines. In this Review, we describe the opportunities of using mRNA–LNPs in oncology applications and discuss the challenges for successfully translating the findings of preclinical studies of these nanoparticles into the clinic. We critically appraise the potential of various mRNA–LNP targeting and delivery strategies, considering physiological, technological and manufacturing challenges. We explore these approaches in the context of the potential clinical applications best suited to each approach and highlight the obstacles that currently need to be addressed to achieve these applications. Finally, we provide insights from preclinical and clinical studies that are leading to this powerful platform being considered the next frontier in oncology treatment.

Key points

  • mRNA–lipid nanoparticles (LNPs) are a powerful, versatile platform that hold great potential as anticancer therapies; LNPs have been tested in clinical applications and can successfully and safely deliver mRNA payloads designed to target various tissues and cell types.

  • mRNA–LNPs can be administered to specific tissues through various routes and using different approaches for targeting specific tissues and cell types.

  • Passive targeting approaches do not involve modifications of mRNA–LNPs for delivery to specific tissues and cells; these approaches typically rely on inherent tendencies of different particles to accumulate in different tissues or tumours.

  • Active targeting approaches involve modification of the surface of mRNA–LNPs for their delivery to a specific cell type; improvements in the ability to target nanoparticles to specific cell types is key for expanding their applications in clinical oncology.

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Fig. 1: mRNA–LNP delivery into cells.
Fig. 2: Strategies for targeting mRNA–LNPs to tumours.
Fig. 3: Strategies to functionalize antibodies on LNPs.
Fig. 4: Future directions for improved targeting strategies.
Fig. 5: Considerations and potential applications of passive and active strategies for targeting tumours with mRNA–LNPs.

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Acknowledgements

E.K. is the recipient of a fellowship from the Yoran Institute for Human Genome Research. D.P. receives funding support from the European Research Council (advanced grant 101055029), The EXPERT project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 825828, ISF grant 2012/20, the Innovation Authority in Israel (Kamin-Corona), and the Shmunis Family Foundation.

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  1. These authors contributed equally: Edo Kon, Nitay Ad-El.

Authors and Affiliations

  1. Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Edo Kon, Nitay Ad-El, Inbal Hazan-Halevy, Lior Stotsky-Oterin & Dan Peer

  2. Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel

    Edo Kon, Nitay Ad-El, Inbal Hazan-Halevy, Lior Stotsky-Oterin & Dan Peer

  3. Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel

    Edo Kon, Nitay Ad-El, Inbal Hazan-Halevy, Lior Stotsky-Oterin & Dan Peer

  4. Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel

    Edo Kon, Nitay Ad-El, Inbal Hazan-Halevy, Lior Stotsky-Oterin & Dan Peer

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E.K. and N.A.-E. researched data for this article. All authors contributed substantially to the discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

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D.P. receives licensing fees (to patents on which he was an inventor), has invested, has consulted, has been on the scientific advisory boards or boards of directors, given paid lectures or conducted research at Tel Aviv University sponsored by ART Biosciences, BioNTech, Earli, Kernal Biologics, Merck, NeoVac, Newphase, Roche, SirTLabs Corporation and Teva Pharmaceuticals. All other authors declare no competing financial interests.

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Kon, E., Ad-El, N., Hazan-Halevy, I. et al. Targeting cancer with mRNA–lipid nanoparticles: key considerations and future prospects. Nat Rev Clin Oncol 20, 739–754 (2023). https://doi.org/10.1038/s41571-023-00811-9

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