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Hybrid core-shell particles for mRNA systemic delivery.

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Title: Hybrid core-shell particles for mRNA systemic delivery.
Authors: Andretto, Valentina1 (AUTHOR), Repellin, Mathieu1 (AUTHOR), Pujol, Marine1 (AUTHOR), Almouazen, Eyad1 (AUTHOR), Sidi-Boumedine, Jacqueline1 (AUTHOR), Granjon, Thierry2 (AUTHOR), Zhang, Heyang3 (AUTHOR), Remaut, Katrien3 (AUTHOR), Jordheim, Lars Petter4 (AUTHOR), Briançon, Stéphanie1 (AUTHOR), Keil, Isabell Sofia5 (AUTHOR), Vascotto, Fulvia5 (AUTHOR), Walzer, Kerstin C.6 (AUTHOR), Sahin, Ugur6 (AUTHOR), Haas, Heinrich6 (AUTHOR), Kryza, David1,7 (AUTHOR), Lollo, Giovanna1 (AUTHOR) giovanna.lollo@univ-lyon1.fr
Source: Journal of Controlled Release. Jan2023, Vol. 353, p1037-1049. 13p.
Subjects: Messenger RNA, Reticulo-endothelial system, Surface charges, Gene expression, Hyaluronic acid, Nucleic acids
Abstract: mRNA based infectious disease vaccines have opened the venue for development of novel nucleic acids-based therapeutics. For all mRNA therapeutics dedicated delivery systems are required, where different functionalities and targeting abilities need to be optimized for the respective applications. One option for advanced formulations with tailored properties are lipid-polymer hybrid nanoparticles with complex nanostructure, which allow to combine features of several already well described nucleic acid delivery systems. Here, we explored hyaluronic acid (HA) as coating of liposome-mRNA complexes (LRCs) to investigate effects of the coating on surface charge, physicochemical characteristics and biological activity. HA was electrostatically attached to positively charged complexes, forming hybrid LRCs (HLRCs). At different N/P ratios, physico-chemical characterization of the two sets of particles showed similarity in size (around 200 nm) and mRNA binding abilities, while the presence of the HA shell conferred a negative surface charge to otherwise positive complexes. High transfection efficiency of LRCs and HLRCs in vitro has been obtained in THP-1 and human monocytes derived from PBMC, an interesting target cell population for cancer and immune related pathologies. In mice, quantitative biodistribution of radiolabeled LRC and HLRC particles, coupled with bioluminescence studies to detect the protein translation sites, hinted towards both particles' accumulation in the hepatic reticuloendothelial system (RES). mRNA translated proteins though was found mainly in the spleen, a major source for immune cells, with preference for expression in macrophages. The results showed that surface modifications of liposome-mRNA complexes can be used to fine-tune nanoparticle physico-chemical characteristics. This provides a tool for assembly of stable and optimized nanoparticles, which are prerequisite for future therapeutic interventions using mRNA-based nanomedicines. [Display omitted] • Lipid-polymer hybrid carriers emerged as next generation systems for gene delivery • Polymer coating can expand the applications of mRNA lipid nanoparticles • In vivo fate of mRNA lipid-based nanoparticles correlates with the lipid composition • A rational design of mRNA delivery systems is crucial to maximize their efficacy • Precise cell population targeting can set the ground for specific applications [ABSTRACT FROM AUTHOR]
Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 161552725
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
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  Data: Hybrid core-shell particles for mRNA systemic delivery.
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  Data: <searchLink fieldCode="AR" term="%22Andretto%2C+Valentina%22">Andretto, Valentina</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Repellin%2C+Mathieu%22">Repellin, Mathieu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pujol%2C+Marine%22">Pujol, Marine</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Almouazen%2C+Eyad%22">Almouazen, Eyad</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sidi-Boumedine%2C+Jacqueline%22">Sidi-Boumedine, Jacqueline</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Granjon%2C+Thierry%22">Granjon, Thierry</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Heyang%22">Zhang, Heyang</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Remaut%2C+Katrien%22">Remaut, Katrien</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jordheim%2C+Lars+Petter%22">Jordheim, Lars Petter</searchLink><relatesTo>4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Briançon%2C+Stéphanie%22">Briançon, Stéphanie</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Keil%2C+Isabell+Sofia%22">Keil, Isabell Sofia</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Vascotto%2C+Fulvia%22">Vascotto, Fulvia</searchLink><relatesTo>5</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Walzer%2C+Kerstin+C%2E%22">Walzer, Kerstin C.</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sahin%2C+Ugur%22">Sahin, Ugur</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Haas%2C+Heinrich%22">Haas, Heinrich</searchLink><relatesTo>6</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kryza%2C+David%22">Kryza, David</searchLink><relatesTo>1,7</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lollo%2C+Giovanna%22">Lollo, Giovanna</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> giovanna.lollo@univ-lyon1.fr</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Controlled+Release%22">Journal of Controlled Release</searchLink>. Jan2023, Vol. 353, p1037-1049. 13p.
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  Data: <searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Reticulo-endothelial+system%22">Reticulo-endothelial system</searchLink><br /><searchLink fieldCode="DE" term="%22Surface+charges%22">Surface charges</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Hyaluronic+acid%22">Hyaluronic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleic+acids%22">Nucleic acids</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: mRNA based infectious disease vaccines have opened the venue for development of novel nucleic acids-based therapeutics. For all mRNA therapeutics dedicated delivery systems are required, where different functionalities and targeting abilities need to be optimized for the respective applications. One option for advanced formulations with tailored properties are lipid-polymer hybrid nanoparticles with complex nanostructure, which allow to combine features of several already well described nucleic acid delivery systems. Here, we explored hyaluronic acid (HA) as coating of liposome-mRNA complexes (LRCs) to investigate effects of the coating on surface charge, physicochemical characteristics and biological activity. HA was electrostatically attached to positively charged complexes, forming hybrid LRCs (HLRCs). At different N/P ratios, physico-chemical characterization of the two sets of particles showed similarity in size (around 200 nm) and mRNA binding abilities, while the presence of the HA shell conferred a negative surface charge to otherwise positive complexes. High transfection efficiency of LRCs and HLRCs in vitro has been obtained in THP-1 and human monocytes derived from PBMC, an interesting target cell population for cancer and immune related pathologies. In mice, quantitative biodistribution of radiolabeled LRC and HLRC particles, coupled with bioluminescence studies to detect the protein translation sites, hinted towards both particles' accumulation in the hepatic reticuloendothelial system (RES). mRNA translated proteins though was found mainly in the spleen, a major source for immune cells, with preference for expression in macrophages. The results showed that surface modifications of liposome-mRNA complexes can be used to fine-tune nanoparticle physico-chemical characteristics. This provides a tool for assembly of stable and optimized nanoparticles, which are prerequisite for future therapeutic interventions using mRNA-based nanomedicines. [Display omitted] • Lipid-polymer hybrid carriers emerged as next generation systems for gene delivery • Polymer coating can expand the applications of mRNA lipid nanoparticles • In vivo fate of mRNA lipid-based nanoparticles correlates with the lipid composition • A rational design of mRNA delivery systems is crucial to maximize their efficacy • Precise cell population targeting can set the ground for specific applications [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Journal of Controlled Release is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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    Identifiers:
      – Type: doi
        Value: 10.1016/j.jconrel.2022.11.042
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      – Code: eng
        Text: English
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        PageCount: 13
        StartPage: 1037
    Subjects:
      – SubjectFull: Messenger RNA
        Type: general
      – SubjectFull: Reticulo-endothelial system
        Type: general
      – SubjectFull: Surface charges
        Type: general
      – SubjectFull: Gene expression
        Type: general
      – SubjectFull: Hyaluronic acid
        Type: general
      – SubjectFull: Nucleic acids
        Type: general
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      – TitleFull: Hybrid core-shell particles for mRNA systemic delivery.
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            – D: 01
              M: 01
              Text: Jan2023
              Type: published
              Y: 2023
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