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Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination
Open accessAbstract
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.
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“The findings of this study revealed that, compared with naked PbAE-mRNA, cellular transfection efficiency was greatly improved when LPP-coated PbAE-mRNA was used.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [326]
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“Moreover, this LPP-based mRNA vaccine exhibited intrinsic adjuvant activity, which stimulates dendritic cells (DCs) to secrete cytokines and inhibit tumor growth by activating the TLR7/8 signaling pathway, resulting in a significant antitumor activity.”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [326]
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Metadata
- Authors
- Persano, S., Guevara, M. L., Li, Z., Mai, J., Ferrari, M., Pompa, P. P., & Shen, H.
- Affiliations
- Houston Methodist (US)
- Italian Institute of Technology (IT)
- Corresponding author
- Shen, Haifa
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 125
- Pages
- 81-89
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC5378555
- OpenAlex
- W2589539207
- Cited by
- 187
- References
- 43
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 30 · 2023: 28 · 2022: 26 · 2021: 18 · 2020: 20 · 2019: 13 · 2018: 12 · 2017: 4
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 296 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R01CA193880-01A1, U54CA210181)
- U.S. Department of Defense (W81XWH-12-1-0414)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mRNA vaccines, lipopolyplexes, poly(β-amino ester), core-shell nanoparticles, dendritic cells, macropinocytosis, interferon-beta, IL-12, antigen presentation, lung metastasis, B16-OVA tumor, antitumor immunity, vaccine adjuvants, lipid shell
- MeSH terms
- Animals, Drug Synergism, Female, Liposomes, Male, Mice, Inbred C57BL, Neoplasms, Experimental, RNA, Messenger, Transfection, Treatment Outcome, Cancer Vaccines, Cell Line, Tumor, Mice
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