No retraction, correction or concern found when last checked on Oct 20, 2026.
Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy
Maria L. Guevara, Francesca Persano, Stefano Persano
Frontiers in Chemistry · 2020 · Review · CC BY
Abstract
Over the past decade, messenger RNA (mRNA) has emerged as potent and flexible platform for the development of novel effective cancer immunotherapies. Advances in non-viral gene delivery technologies, especially the tremendous progress in lipid nanoparticles’ manufacturing, have made possible the implementation of mRNA-based antitumor treatments. Several mRNA-based immunotherapies have demonstrated antitumor effect in preclinical and clinical studies, and marked successes have been achieved most notably by its implementation in therapeutic vaccines, cytokines therapies, checkpoint blockade and chimeric antigen receptor (CAR) cell therapy. In this review, we summarize recent advances in the development of lipid nanoparticles for mRNA-based immunotherapies and their applications in cancer treatment. Finally, we also highlight the variety of immunotherapeutic approaches through mRNA delivery and discuss the main factors affecting transfection efficiency and tropism of mRNA-loaded lipid nanoparticles in vivo.
References 97
- 1.
Arteta M. Y. Kjellman T. Bartesaghi S. Wallin S. Wu X. Kvist A. J. (2018 ). Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 115, E3351–E3360.
Not in our library10.1073/pnas.1720542115
- 2.
Bailey A. L. Cullis P. R. (1994 ). Modulation of membrane fusion by asymmetric transbilayer distributions of amino lipids. Biochemistry 33, 12573–12580.
Not in our library10.1021/bi00208a007
- 3.
Baldin A. V. Savvateeva L. V. Bazhin A. V. Zamyatnin A. A. Jr (2020 ). Dendritic cells in anticancer vaccination: rationale for ex vivo loading or in vivo targeting. Cancers 12:590
Not in our library10.3390/cancers12030590
- 4.
Ball R. L. Hajj K. A. Vizelman J. Bajaj P. Whitehead K. A. (2018 ). Lipid nanoparticle formulations for enhanced co-delivery of siRNA and mRNA. Nano Lett. 18, 3814–3822.
Not in our library10.1021/acs.nanolett.8b01101
- 5.
Belliveau N. M. Huft J. Lin P. J. C. Chen S. Leung A. K. K. Leaver T. J.. (2012 ). Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol. Ther. Nucleic Acids 1:e37.
Not in our library10.1038/mtna.2012.28
- 6.
Billingsley M. M. Singh N. Ravikumar P. Zhang R. June C. H. Mitchell M. J. (2020 ). Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett. 20, 1578–1589.
Not in our library10.1021/acs.nanolett.9b04246
- 7.
- 8.
Blanco E. Shen H. Ferrari M. (2015 ). Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951.
Not in our library10.1038/nbt.3330
- 9.
Brudno J. N. Kochenderfer J. N. (2016 ). Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 127, 3321–3330.
Not in our library10.1182/blood-2016-04-703751
- 10.
Cheng Q. Wei T. Farbiak L. Johnson L. T. Dilliard S. A. Siegwart D. J. (2020 ). Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313–320.
Not in our library10.1038/s41565-020-0669-6
- 11.
- 12.
Cullis P. R. Hope M. J. (2017 ). Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 25, 1467–1475.
Not in our library10.1016/j.ymthe.2017.03.013
- 13.
De Beuckelaer A. Pollard C. Van Lint S. Roose K. Van Hoecke L. Naessens T.. (2016 ). Type I interferons interfere with the capacity of mRNA lipoplex vaccines to elicit cytolytic T cell responses. Mol. Ther. 24, 2012–2020.
Not in our library10.1038/mt.2016.161
- 14.
Eygeris Y. Patel S. Jozic A. Sahay G. (2020 ). Deconvoluting lipid nanoparticle structure for messenger RNA delivery. Nano Lett. 20, 4543–4549.
Not in our library10.1021/acs.nanolett.0c01386
- 15.
- 16.
Felgner P. L. Ringold G. M. (1989 ). Cationic liposome-mediated transfection. Nature 337, 387–388.
Not in our library10.1038/337387a0
- 17.
Fenton O. S. Kauffman K. J. McClellan R. L. Appel E. A. Dorkin J. R. Tibbitt M. W.. (2016 ). Bioinspired alkenyl amino alcohol ionizable lipid materials for highly potent in vivo mRNA delivery. Adv. Mater. 28, 2939–2943.
Not in our library10.1002/adma.201505822
- 18.
Foster J. B. Barrett D. M. Karikó K. (2019 ). The emerging role of in vitro-transcribed mRNA in adoptive T cell immunotherapy. Mol Ther. 27, 747–756.
Not in our library10.1016/j.ymthe.2019.01.018
- 19.
Gall D. (1966 ). The adjuvant activity of aliphatic nitrogenous bases. Immunology 11, 369–386.
Not in our library
- 20.
Gilleron J. Querbes W. Zeigerer A. Borodovsky A. Marsico G. Schubert U.. (2013 ). Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31, 638–646.
Not in our library10.1038/nbt.2612
- 21.
- 22.
Granot Y. Peer D. (2017 ). Delivering the right message: challenges and opportunities in lipid nanoparticles-mediated modified mRNA therapeutics-An innate immune system standpoint. Semin. Immunol. 34, 68–77.
Not in our library10.1016/j.smim.2017.08.015
- 23.
Guan S. Rosenecker J. (2017 ). Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 24, 133–143.
Not in our library10.1038/gt.2017.5
- 24.
Guevara M. L. Jilesen Z. Stojdl D. Persano S. (2019a ). Codelivery of mRNA with α-Galactosylceramide using a new lipopolyplex formulation induces a strong antitumor response upon intravenous administration. ACS Omega 4, 13015–13026.
Not in our library10.1021/acsomega.9b00489
- 25.
Guevara M. L. Persano S. Persano F. (2019b ). Lipid-based vectors for therapeutic mRNA-based anti-cancer vaccines. Curr Pharm Des. 25, 1443–1454.
Not in our library10.2174/1381612825666190619150221
- 26.
Haabeth O. A. W. Blake T. R. McKinlay C. J. Tveita A. A. Sallets A. Waymouth R. M.. (2019 ). Local delivery of Ox40l, Cd80, and Cd86 mRNA kindles global anticancer immunity. Cancer Res. 79, 1624–1634.
Not in our library10.1158/0008-5472.can-18-2867
- 27.
Hajj K. A. Whitehead K. A. (2017 ). Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2:17056
Not in our library10.1038/natrevmats.2017.56
- 28.
Harper P. E. Mannock D. A. Lewis R. N. A. H. McElhaney R. N. Gruner S. (2001 ). X-ray diffraction of some phosphatidylethanolamine lamellar and inverted hexagonal phases. Biophys. J. 81, 2693–2706.
Not in our library10.1016/s0006-3495(01)75912-7
- 29.
- 30.
Henriksen-Lacey M. Christensen D. Bramwell V. W. Lindenstrom T. Agger E. M. Andersen P.. (2010 ). Liposomal cationic charge and antigen adsorption are important properties for the efficient deposition of antigen at the injection site and ability of the vaccine to induce a cmi response. J. Control Release 145, 102–108.
Not in our library10.1016/j.jconrel.2010.03.027
- 31.
- 32.
Holtkamp S. Kreiter S. Selmi A. Simon P. Koslowski M. Huber C.. (2006 ). Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. Blood 108, 4009–4017.
Not in our library10.1182/blood-2006-04-015024
- 33.
Islam M. A. Xu Y. Tao W. Ubellacker J. M. Lim M. Aum D. (2018 ). Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat. Biomed. Eng. 2, 850–864.
Not in our library10.1038/s41551-018-0284-0
- 34.
Jackson H. J. Rafiq S. Brentjens R. J. (2016 ). Driving CAR T-cells forward. Nat. Rev. Clin. Oncol. 13, 370–383.
Not in our library10.1038/nrclinonc.2016.36
- 35.
- 36.
Judge A. McClintock K. Phelps J. R. MacLachlan I. (2006 ). Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. Mol. Ther. 13, 328–337.
Not in our library10.1016/j.ymthe.2005.09.014
- 37.
- 38.
Kaczmarek J. C. Patel A. K. Kauffman K. J. Fenton O. S. Webber M. J. Heartlein M. W.. (2016 ). Polymer-lipid nanoparticles for systemic delivery of mRNA to the lungs. Angew. Chem. Int. Ed. Engl. 55, 13808–13812.
Not in our library10.1002/anie.201608450
- 39.
Karikó K. Muramatsu H. Ludwig J. Weissman D. (2011 ). Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 39:e142.
Not in our library10.1093/nar/gkr695
- 40.
Kon E. Hazan-Halevy I. Rosenblum D. Cohen N. Chatterjee S. Veiga N.. (2020 ). Resveratrol enhances mRNA and siRNA lipid nanoparticles primary CLL cell transfection. Pharmaceutics 12:520.
Not in our library10.3390/pharmaceutics12060520
Cited by papers we hold 7
- mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications · 2023No notice
- Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics · 2023No notice
- Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects · 2022No notice
- mRNA-based therapeutics: powerful and versatile tools to combat diseases · 2022No notice
- mRNA vaccines for cancer immunotherapy · 2022No notice
- A Survey of Preclinical Studies Evaluating Nanoparticle-Based Vaccines Against Non-Viral Sexually Transmitted Infections · 2021Not checked
- A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems · 2021No notice
Reads
Read by people on this page
None yet.
Checked or read by AI through naulon
None yet.
A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.
Are you an author?
Is this your paper?
Claim it to add your note and be paid when agents cite it. Free.