Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus (2024)

Maeshima, R., Tagalakis, A. D., Gyftaki-Venieri, D., Jones, S. A., Rye, P. D., Tøndervik, A., Åstrand, O. A. H., & Hart, S. L. (2024). Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus. Advanced healthcare materials, 1-14. Advance online publication. https://doi.org/10.1002/adhm.202400510

Maeshima, Ruhina ; Tagalakis, Aristides D. ; Gyftaki-Venieri, Dafni et al. / Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus. In: Advanced healthcare materials. 2024 ; pp. 1-14.

@article{f51e34cff70b411d9b16086ccc7ea6db,

title = "Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus",

abstract = "Airway mucus is a major barrier to the delivery of lipid-based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor-Targeted Nanocomplexes (RTN), comprise mixtures of cationic lipids and bifunctional peptides with receptor-targeting and nucleic acid packaging properties. The aim of this study is to improve the mucus-penetrating properties of cationic siRNA and mRNA RTNs by combining them with low molecular weight alginate oligosaccharides, OligoG and OligoM. Cationic RTNs formulated with either alginate become strongly anionic, while PEGylated messenger RNA (mRNA) and short interfering RNA (siRNA) RTNs remain cationic. Both alginates enhance mucus diffusion rates of cationic siRNA and mRNA RTNs in a static mucus barrier diffusion model, with OligoG particularly effective. PEGylation also enhance mucus diffusion rates of siRNA RTNs but not mRNA RTNs. Electron microscopy shows that RTNs remained intact after mucosal transit. The transfection efficiency of OligoM-coated mRNA RTNs is better than those coated with OligoG or PEG, and similar to cationic RTNs. In siRNA RTN transfections, OligoM is better than OligoG although 1% PEG is slightly better than both. The combination of cationic RTNs and alginate oligosaccharides represents a promising alternative to PEGylation for epithelial delivery of genetic therapies across the mucus barrier while retaining transfection efficiency.",

keywords = "cystic fibrosis, mRNA, mucus penetration, nanoparticles, siRNA",

author = "Ruhina Maeshima and Tagalakis, {Aristides D.} and Dafni Gyftaki-Venieri and Jones, {Stuart A.} and Rye, {Philip D.} and Anne T{\o}ndervik and {\AA}strand, {O. Alexander H.} and Hart, {Stephen L.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.",

year = "2024",

month = nov,

day = "13",

doi = "10.1002/adhm.202400510",

language = "English",

pages = "1--14",

journal = "Advanced healthcare materials",

issn = "2192-2640",

publisher = "John Wiley and Sons Ltd",

}

Maeshima, R, Tagalakis, AD, Gyftaki-Venieri, D, Jones, SA, Rye, PD, Tøndervik, A, Åstrand, OAH & Hart, SL 2024, 'Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus', Advanced healthcare materials, pp. 1-14. https://doi.org/10.1002/adhm.202400510

Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus. / Maeshima, Ruhina; Tagalakis, Aristides D.; Gyftaki-Venieri, Dafni et al.
In: Advanced healthcare materials, 13.11.2024, p. 1-14.

Research output: Contribution to journal › Article (journal) › peer-review

TY - JOUR

T1 - Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus

AU - Maeshima, Ruhina

AU - Tagalakis, Aristides D.

AU - Gyftaki-Venieri, Dafni

AU - Jones, Stuart A.

AU - Rye, Philip D.

AU - Tøndervik, Anne

AU - Åstrand, O. Alexander H.

AU - Hart, Stephen L.

N1 - Publisher Copyright:© 2024 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.

PY - 2024/11/13

Y1 - 2024/11/13

N2 - Airway mucus is a major barrier to the delivery of lipid-based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor-Targeted Nanocomplexes (RTN), comprise mixtures of cationic lipids and bifunctional peptides with receptor-targeting and nucleic acid packaging properties. The aim of this study is to improve the mucus-penetrating properties of cationic siRNA and mRNA RTNs by combining them with low molecular weight alginate oligosaccharides, OligoG and OligoM. Cationic RTNs formulated with either alginate become strongly anionic, while PEGylated messenger RNA (mRNA) and short interfering RNA (siRNA) RTNs remain cationic. Both alginates enhance mucus diffusion rates of cationic siRNA and mRNA RTNs in a static mucus barrier diffusion model, with OligoG particularly effective. PEGylation also enhance mucus diffusion rates of siRNA RTNs but not mRNA RTNs. Electron microscopy shows that RTNs remained intact after mucosal transit. The transfection efficiency of OligoM-coated mRNA RTNs is better than those coated with OligoG or PEG, and similar to cationic RTNs. In siRNA RTN transfections, OligoM is better than OligoG although 1% PEG is slightly better than both. The combination of cationic RTNs and alginate oligosaccharides represents a promising alternative to PEGylation for epithelial delivery of genetic therapies across the mucus barrier while retaining transfection efficiency.

AB - Airway mucus is a major barrier to the delivery of lipid-based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor-Targeted Nanocomplexes (RTN), comprise mixtures of cationic lipids and bifunctional peptides with receptor-targeting and nucleic acid packaging properties. The aim of this study is to improve the mucus-penetrating properties of cationic siRNA and mRNA RTNs by combining them with low molecular weight alginate oligosaccharides, OligoG and OligoM. Cationic RTNs formulated with either alginate become strongly anionic, while PEGylated messenger RNA (mRNA) and short interfering RNA (siRNA) RTNs remain cationic. Both alginates enhance mucus diffusion rates of cationic siRNA and mRNA RTNs in a static mucus barrier diffusion model, with OligoG particularly effective. PEGylation also enhance mucus diffusion rates of siRNA RTNs but not mRNA RTNs. Electron microscopy shows that RTNs remained intact after mucosal transit. The transfection efficiency of OligoM-coated mRNA RTNs is better than those coated with OligoG or PEG, and similar to cationic RTNs. In siRNA RTN transfections, OligoM is better than OligoG although 1% PEG is slightly better than both. The combination of cationic RTNs and alginate oligosaccharides represents a promising alternative to PEGylation for epithelial delivery of genetic therapies across the mucus barrier while retaining transfection efficiency.

KW - cystic fibrosis

KW - mRNA

KW - mucus penetration

KW - nanoparticles

KW - siRNA

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UR - http://www.scopus.com/inward/citedby.url?scp=85208808754&partnerID=8YFLogxK

U2 - 10.1002/adhm.202400510

DO - 10.1002/adhm.202400510

M3 - Article (journal)

AN - SCOPUS:85208808754

SN - 2192-2640

SP - 1

EP - 14

JO - Advanced healthcare materials

JF - Advanced healthcare materials

ER -

Maeshima R, Tagalakis AD, Gyftaki-Venieri D, Jones SA, Rye PD, Tøndervik A et al. Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus. Advanced healthcare materials. 2024 Nov 13;1-14. Epub 2024 Nov 13. doi: 10.1002/adhm.202400510