Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics
Abstract Lipid Nanoparticles (LNPs) recently emerged as an invaluable RNA delivery platform. With many LNP‐based therapeutics in the pre‐clinical and clinical pipelines, there is extensive research dedicated to improving LNPs. These efforts focus mainly on the tolerability and transfectability of ne...
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2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408744 |
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| author | Riccardo Rampado Gonna Somu Naidu Olga Karpov Meir Goldsmith Preeti Sharma Assaf Ezra Lior Stotsky Dor Breier Dan Peer |
| author_facet | Riccardo Rampado Gonna Somu Naidu Olga Karpov Meir Goldsmith Preeti Sharma Assaf Ezra Lior Stotsky Dor Breier Dan Peer |
| author_sort | Riccardo Rampado |
| collection | DOAJ |
| description | Abstract Lipid Nanoparticles (LNPs) recently emerged as an invaluable RNA delivery platform. With many LNP‐based therapeutics in the pre‐clinical and clinical pipelines, there is extensive research dedicated to improving LNPs. These efforts focus mainly on the tolerability and transfectability of new ionizable lipids and RNAs, or modulating LNPs biodistribution with active targeting strategies. However, most formulations follow the well‐established lipid proportions used in clinically approved products. Nevertheless, investigating the effects of LNPs composition on their biodistribution can expand the toolbox for particle design, leading to improved delivery strategies. Herein, a new LNPs (30‐n‐LNPs) formulation with increasing amounts of phospholipids is investigated as a possible mRNA delivery system for treating Inflammatory Bowel Diseases. Compared to LNPs with benchmark composition (b‐LNPs), n‐LNPs containing 30% distearoylphosphatidylcholine (DSPC) are well tolerated following intravenous administration and display natural targeting toward the inflamed colon in dextran sodium sulfate (DSS)‐colitis bearing mice, while de‐targeting clearing organs such as the liver and spleen. Using interleukin‐10‐encoding mRNA as therapeutic cargo, n‐LNPs demonstrated a reduction of pathological burden in colitis‐bearing mice. n‐LNPs represent a starting point to further investigate the influence of LNPs composition on systemic biodistribution, ultimately opening new therapeutic modalities in different pathologies. |
| format | Article |
| id | doaj-art-f968c49a919b47b189577ee709728981 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
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| spelling | doaj-art-f968c49a919b47b189577ee7097289812025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202408744Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA TherapeuticsRiccardo Rampado0Gonna Somu Naidu1Olga Karpov2Meir Goldsmith3Preeti Sharma4Assaf Ezra5Lior Stotsky6Dor Breier7Dan Peer8Laboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelLaboratory of Precision Nanomedicine Shmunis School of Biomedicine and Cancer Research Tel Aviv University Tel Aviv‐Yafo 69978 IsraelAbstract Lipid Nanoparticles (LNPs) recently emerged as an invaluable RNA delivery platform. With many LNP‐based therapeutics in the pre‐clinical and clinical pipelines, there is extensive research dedicated to improving LNPs. These efforts focus mainly on the tolerability and transfectability of new ionizable lipids and RNAs, or modulating LNPs biodistribution with active targeting strategies. However, most formulations follow the well‐established lipid proportions used in clinically approved products. Nevertheless, investigating the effects of LNPs composition on their biodistribution can expand the toolbox for particle design, leading to improved delivery strategies. Herein, a new LNPs (30‐n‐LNPs) formulation with increasing amounts of phospholipids is investigated as a possible mRNA delivery system for treating Inflammatory Bowel Diseases. Compared to LNPs with benchmark composition (b‐LNPs), n‐LNPs containing 30% distearoylphosphatidylcholine (DSPC) are well tolerated following intravenous administration and display natural targeting toward the inflamed colon in dextran sodium sulfate (DSS)‐colitis bearing mice, while de‐targeting clearing organs such as the liver and spleen. Using interleukin‐10‐encoding mRNA as therapeutic cargo, n‐LNPs demonstrated a reduction of pathological burden in colitis‐bearing mice. n‐LNPs represent a starting point to further investigate the influence of LNPs composition on systemic biodistribution, ultimately opening new therapeutic modalities in different pathologies.https://doi.org/10.1002/advs.202408744colongenetic medicinesinflammatory bowel diseaselipid nanoparticlesmRNAtargeting |
| spellingShingle | Riccardo Rampado Gonna Somu Naidu Olga Karpov Meir Goldsmith Preeti Sharma Assaf Ezra Lior Stotsky Dor Breier Dan Peer Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics Advanced Science colon genetic medicines inflammatory bowel disease lipid nanoparticles mRNA targeting |
| title | Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics |
| title_full | Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics |
| title_fullStr | Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics |
| title_full_unstemmed | Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics |
| title_short | Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics |
| title_sort | lipid nanoparticles with fine tuned composition show enhanced colon targeting as a platform for mrna therapeutics |
| topic | colon genetic medicines inflammatory bowel disease lipid nanoparticles mRNA targeting |
| url | https://doi.org/10.1002/advs.202408744 |
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